Insulin-treated Diabetes Research Articles

Incidence and costs of hypoglycemia in insulin-treated diabetes in Switzerland: A health-economic analysis

AimsWe assess the incidence and economic burden of severe and non-severe hypoglycemia in insulin-treated diabetes type 1 and 2 patients in Switzerland. MethodsWe developed a health economic model to assess the incidence of hypoglycemia, the subsequent medical costs, and the production losses in insulin-treated diabetes patients. The model distinguishes between severity of hypoglycemia, type of diabetes, and type of medical care. We used survey data, health statistics, and health care utilization data extracted from primary studies. ResultsThe number of hypoglycemic events in 2017 was estimated at 1.3 million in type 1 diabetes patients and at 0.7 million in insulin-treated type 2 diabetes patients. The subsequent medical costs amount to 38 million Swiss Francs (CHF), 61 % of which occur in type 2 diabetes. Outpatient visits dominate costs in both types of diabetes. Total production losses due to hypoglycemia amount to CHF 11 million. Almost 80 % of medical costs and 39 % of production losses are due to non-severe hypoglycemia. ConclusionsHypoglycemia leads to substantial socio-economic burden in Switzerland. Greater attention to non-severe hypoglycemic events and to severe hypoglycemia in type 2 diabetes could have a major impact on reducing this burden.

Psychometric properties of an innovative smartphone application to investigate the daily impact of hypoglycemia in people with type 1 or type 2 diabetes: The Hypo-METRICS app.

The aim of this study was to determine the acceptability and psychometric properties of the Hypo-METRICS (Hypoglycemia MEasurement, ThResholds and ImpaCtS) application (app): a novel tool designed to assess the direct impact of symptomatic and asymptomatic hypoglycemia on daily functioning in people with insulin-treated diabetes. 100 adults with type 1 diabetes mellitus (T1DM, n = 64) or insulin-treated type 2 diabetes mellitus (T2DM, n = 36) completed three daily 'check-ins' (morning, afternoon and evening) via the Hypo-METRICs app across 10 weeks, to respond to 29 unique questions about their subjective daily functioning. Questions addressed sleep quality, energy level, mood, affect, cognitive functioning, fear of hypoglycemia and hyperglycemia, social functioning, and work/productivity. Completion rates, structural validity, internal consistency, and test-retest reliability were explored. App responses were correlated with validated person-reported outcome measures to investigate convergent (rs>±0.3) and divergent (rs<±0.3) validity. Participants' mean±SD age was 54±16 years, diabetes duration was 23±13 years, and most recent HbA1c was 56.6±9.8 mmol/mol. Participants submitted mean±SD 191±16 out of 210 possible 'check-ins' (91%). Structural validity was confirmed with multi-level confirmatory factor analysis showing good model fit on the adjusted model (Comparative Fit Index >0.95, Root-Mean-Square Error of Approximation <0.06, Standardized Root-Mean-square Residual<0.08). Scales had satisfactory internal consistency (all ω≥0.5), and high test-retest reliability (rs≥0.7). Convergent and divergent validity were demonstrated for most scales. High completion rates and satisfactory psychometric properties demonstrated that the Hypo-METRICS app is acceptable to adults with T1DM and T2DM, and a reliable and valid tool to explore the daily impact of hypoglycemia.

Impact of Insulin-Treated Compared to Non-Insulin-Treated Diabetes Mellitus on Outcome of Percutaneous Coronary Intervention with Drug-Coated Balloons versus Drug-Eluting Stents in De Novo Coronary Artery Disease: The Randomized BASKET-SMALL 2 Trial.

We evaluated the outcome of PCI of de novo stenosis with drug-coated balloons (DCB) versus drug-eluting stents (DES) in patients with insulin-treated diabetes mellitus (ITDM) versus non-insulin-treated diabetes mellitus (NITDM). Patients were randomized in the BASKET-SMALL 2 trial to DCB or DES and followed over 3 years for MACE (cardiac death, non-fatal myocardial infarction [MI], and target vessel revascularization [TVR]). Outcome in the diabetic subgroup (n = 252) was analyzed with respect to ITDM or NITDM. In NITDM patients (n = 157), rates of MACE (16.7% vs. 21.9%, hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.29-1.58, p = 0.37), death, non-fatal MI, and TVR (8.4% vs. 14.5%, HR 0.30, 95% CI 0.09-1.03, p = 0.057) were similar between DCB and DES. In ITDM patients (n = 95), rates of MACE (DCB 23.4% vs. DES 22.7%, HR 1.12, 95% CI 0.46-2.74, p = 0.81), death, non-fatal MI, and TVR (10.1% vs. 15.7%, HR 0.64, 95% CI 0.18-2.27, p = 0.49) were similar between DCB and DES. TVR was significantly lower with DCB versus DES in all diabetic patients (HR 0.41, 95% CI 0.18-0.95, p = 0.038). DCB compared to DES for treatment of de novo coronary lesions in diabetic patients was associated with similar rates of MACE and numerically lower need for TVR both for ITDM and NITDM patients.

Development and Validation of a Distress Measurement Related to Glucose Monitoring of Diabetes Patients.

Glucose monitoring-related problems affect the social and psychological distress experienced by patients with diabetes, and this distress leads to low compliance. Consequently, it is important to be able to comprehensively assess distress due to glucose monitoring in these patients. We have developed and validated a distress of self-glucose monitoring (DSGM) scale instrument to assess patient distress from glucose monitoring. Following an extensive literature review and qualitative study, we selected 21 items for assessing the DSGM, including physical, psychosocial, and process domains. We conducted a cross-sectional study in patients with insulin-treated diabetes aged 10-40years at Samsung Medical Center, Seoul, Korea, from April 2021 to September 2021. Exploratory and confirmatory factor analyses (CFA) were performed to confirm the structural validity of the DSGM scale. To confirm construct and criterion validity, we assumed that the Korean version of the Problem Areas in Diabetes (PAID-K) instrument, life interference, and stress due to glucose monitoring might moderately correlate with the total score and scores of all domains of the DSGM scale except for the physical domain. Cronbach's alpha coefficients for the DSGM scale were 0.92, and Cronbach's alpha coefficients of the three subscales ranged from 0.69 to 0.92, indicating satisfactory internal consistency. The DSGM scale was evaluated using CFA, and the fit indices for this model were good. The PAID-K total score, life interference, and stress due to glucose monitoring were moderately correlated with the total score of the DSGM scale and with the scores of the psychosocial and process domains, and were weakly correlated with the score of the physical domain of the DSGM scale. The DSGM scale is a valid and reliable tool to evaluate distress due to glucose monitoring in adults, adolescents, and children with diabetes.

Comparison of Fractional Flow Reserve with Resting Non-Hyperemic Indices in Patients with Coronary Artery Disease.

Guidelines recommend using hyperemic (FFR) and non-hyperemic (iFR/RFR) methods of evaluating coronary artery stenoses in patients with coronary artery disease. However, in some cases, achieved results indicating significant ischemia may differ between those methods. Thus, we sought to identify predictors of such a discrepancy. Data were collected on all consecutive patients with chronic coronary syndrome hospitalized between 2020 and 2021. For 279 patients (417 vessels), results for both FFR and iFR/RFR were available. Values of ≤0.80 for FFR and ≤0.89 for iFR/RFR were considered positive for ischemia. Discordant measurements of FFR and iFR/RFR were observed in 80 (19.2%) patients. Atrial fibrillation was the only predictor of the overall FFR and iFR/RFR discordance - OR (95%CI) 1.90 (1.02-3.51); p = 0.040. The chance of positive FFR and negative iFR/RFR decreased independently with age - OR (95%CI) 0.96 (0.93-0.99); p = 0.024. On the contrary, insulin-treated diabetes mellitus was the predictor of negative FFR and positive iFR/RFR discrepancy - OR (95%CI) 4.61 (1.38-15.40); p = 0.013. In everyday clinical practice, iFR/FFR correlates well with FFR. However, discordance between these methods is quite common. Physicians should be aware of the risk of such discordance in patients with atrial fibrillation, advanced age, and insulin-treated diabetes mellitus.

Effect of COVID-19 on cardiac surgery volumes in Sweden

Objectives. The coronavirus disease 2019 (COVID-19) pandemic, which commenced in 2020, is known to frequently cause respiratory failure requiring intensive care, with occasional fatal outcomes. In this study, we aimed to conduct a retrospective nationwide observational study on the influence of the pandemic on cardiac surgery volumes in Sweden. Results. In 2020, 9.4% (n = 539) fewer patients underwent open-heart operations in Sweden (n = 5169) than during 2019 (n = 5708), followed by a 5.8% (n = 302) increase during 2021 (n = 5471). The reduction was greater than 15% in three of the eight hospitals in Sweden performing open-heart operations. Compared to 2019, in 2020, the waiting times for surgery were longer, and the patients were slightly younger, had better renal function, and a lower European System for Cardiac Operative Risk Evaluation; moreover, few patients had a history of myocardial infarction. However, more patients had insulin-treated diabetes mellitus, hypertension, peripheral vascular disease, reduced left ventricular function, and elevated pulmonary artery pressure. Urgent procedures were more common, but acute surgery was less common in 2020 than in 2019. Early mortality and postoperative complications were low and did not differ during the three years. Conclusion. The 9.4% decrease in the number of heart surgeries performed in Sweden during the 2020 COVID-19 pandemic, compared to 2019, partially recovered during 2021; however, there was no backlog of patients awaiting heart surgery.

The effect of couple supportive counseling on self-efficacy in women with insulin-treated gestational diabetes: A randomized clinical trial.

Gestational diabetes is the most common medical complication and a common metabolic disorder during pregnancy. Increasing people's self-efficacy is one of the best ways to control this disease. As there is a lag of intervention in this regard, the purpose of this study was to determine the effect of couple supportive counseling on self-efficacy in women with insulin-treated gestational diabetes. In this randomized clinical trial, 64 women with gestational diabetes who referred to diabetes clinic of Mashhad Ommolbanin Hospital were divided into intervention and control groups through block randomization during 2019. Their gestational age was in 26-30 weeks. For the couples in the intervention group, three couple supportive counseling session was held. Each session lasted 1 h and was held one time per week. The instruments were diabetes self-efficacy questionnaire, fasting and 2-h postprandial checklist and Cassidy social support, which were assessed before and 4 weeks after intervention in both groups. Data was analyzed by SPSS software version 25 through Mann-Whitney and Wilcoxon test. P values of < 0.05 were reported to be significant. In the preintervention, the diabetes self-efficacy score had no significant difference in the intervention (30/6 ± 38/50) and control groups (09/8 ± 56/51) (P = 515/0). However, in the postintervention, the diabetes self-efficacy score was significantly higher in the intervention group (58/6 ± 41/71) compared to the control group (15/7 ± 31/51) (P < 001/0). Also, before the intervention, there was no significant difference between the intervention (30/2 ± 72/10) and control group (87/1 ± 63/11) (P = 137/0) regarding social support. However, after the intervention, there was a significant difference between the intervention and control groups (879/0 ± 53/13, 03/2 ± 41/11, P < 0/001 respectively). Also, data analysis showed a significant correlation between self-efficacy and social support (r = 0.451, P < 0.001), self-efficacy and fasting blood sugar (P < 0.001, r = -0.577), and 2 h post prandial (r = -0.778, P < 0.001). Couple supportive counseling leads to increased self-efficacy and social support in pregnant women with gestational diabetes. Therefore, it is recommended to use this counseling as an effective method in the management of diabetic pregnant women during their prenatal care to have a healthier pregnancy.

Lipohypertrophy prevalence and its associated risk factors in insulin-treated patients with type 2 diabetes in North Borneo, Malaysia.

Insulin-treated diabetes patients are at high risk of developing lipohypertrophy, which can negatively impact treatment outcomes. Early detection of lipohypertrophy is crucial to preventing blood glucose fluctuation. Unfortunately, this clinical issue is often overlooked by nurses, causing the development of vascular complications, which leads to an increase in the morbidity and mortality of the type 2 diabetes mellitus population. This study was conducted to identify lipohypertrophy prevalence and to establish the association between the presence of lipohypertrophy and its associated risk factors, including years on injection, total injection in a day, total insulin unit per day, often change needle, insulin injection site and move to a different area. This cross-sectional study included 128 patients with type 2 diabetes mellitus who received insulin therapy in an outpatient diabetic clinic. Questionnaires on socio-demographic and lipohypertrophy-associated risk factors were distributed among patients, and lipohypertrophy-assessment was done using a checklist. Descriptive statistics and Pearson Chi-square were used for statistical analysis. The prevalence of lipohypertrophy was 51.6% (95% CI: 42.6, 60.5). Swelling on fatty tissue (46.1%) exhibited the highest percentage of lipohypertrophy features during the assessment. Pearson Chi-Square revealed a significant relationship between the presence of LH and BMI categories (χ2 = 10.059, df = 3, p = 0.018), duration of injection (χ2 = 15.001, df = 3, p = 0.002), frequency of needle replacement (χ2 = 9.525, df = 3, p = 0.023) and rotation of injection site (χ2 = 5.914, df = 1, p = 0.015). The high prevalence of lipohypertrophy indicates a need for a prevention strategy. Thus, nurses should play an important role in educating patients regarding the proper administration of insulin injections and performing a routine lipohypertrophy assessment and health education on the correct method of insulin injection.

Teriparatide in a patient with severe osteoporosis, hypoparathyroidism and thalassemia major

β-Thalassemia Major (TM) is a form of beta-thalassemias. TM complications include, among others, osteoporosis, whose frequency, among TM patients, varies from 13.6% to 50%. The overall etiological mechanisms of TM-related osteoporosis remain unclarified. The primary approach to osteoporosis in patients with TM is the management of TM and its complications and the use of antiresorptive agents, such as Bisphosphonates (BPs), as the first line-drug of treatment. In this article, we present the case of 45 years old-woman with TM and severe osteoporosis, with multiple fractures, albeit the assumption of BPs for many years. The anti-fracture efficacy and safety of BPs are not well-established in TM patients. Data suggest that etidronate and zoledronic acid should be considered as first-line agents in the management of TM- associated osteoporosis. Regarding Teriparatide (TP), there are only a few case reports published about its use in TM patients. It is also noticed that, at the dismission of TP therapy, its benefits are rapidly lost. Finally, regarding romosozumab, our patient presents a significant cardiovascular risk due to the presence of insulin-treated Diabetes Mellitus (DM) and TM-related cardiomyopathy, suggesting we avoid this drug. This case report shows that the therapy of osteoporosis in patients with TM remains an open problem. TM patients often present multiple comorbidities which create limitations to osteoporosis’s treatment. Moreover, these comoboridites are often unavoidable risk factors for osteoporosis.

Assessment of Glucose Monitoring Adherence in Medicare Beneficiaries with Insulin-Treated Diabetes.

Background: We investigated the potential associations between race/ethnicity and adherence to prescribed glucose monitoring in a sample of Medicare beneficiaries with diabetes and how adherence to the method used impacted diabetes-related inpatient hospitalizations and associated costs among beneficiaries with intensive insulin-treated diabetes. Methods: This 12-month retrospective analysis utilized Centers for Medicare & Medicaid Services data to identify Medicare beneficiaries who used intensive insulin therapy from January through December 2018 and classified them into four groups: (1) persons using real-time continuous glucose monitoring (rtCGM), (2) persons using any method of blood glucose monitoring (BGM) who followed prescribed use patterns (adherent), (3) persons who were prescribed BGM but were nonadherent in its use, and (4) no record of any form of BGM. Analyses compared these groups and the role that comorbidities (Charlson Comorbidity Index [CCI]), and race/ethnicity played on group assignment, diabetes-related inpatient hospitalizations, and costs. Results: Among the 1,329,061 persons assessed, 38.14% had no record of glucose monitoring and 35.42% were BGM nonadherent. Similarly, among the 629,514 beneficiaries with a CCI risk score of ≥2, 466,646 (74.13%) were either nonadherent to BGM or had no monitoring record. The percentage of White (3.65%) rtCGM adherent beneficiaries was significantly larger than Black (1.58%) and Hispanic (1.28%) beneficiaries, both P < 0.0001. Hospitalizations and costs were higher for Black and Hispanic beneficiaries versus Whites within the risk score ≥ 2 group regardless of glucose monitoring method. Conclusions: Race is associated with increased hospitalizations and costs associated with diabetes care and absence of any form of BGM was associated with higher rates of comorbidities. Persons of color were less likely to use rtCGM despite Medicare coverage. New initiatives that promote diabetes self-management education and support services are needed to improve utilization of glucose monitoring within the Medicare diabetes population.

Insulin Injection-Related Skin Lipodystrophies: Blemish or Pathology?

The number of adult individuals with insulin-treated diabetes mellitus (DM) is steadily increasing worldwide. The main local complications of insulin injection are lipohypertrophies (LHs), i.e., subcutaneous nodules consisting of aggregates of macro-adipocytes and fibrin. These nodules result from errors repeatedly made by patients while injecting insulin. Despite being very common, LH lesions/nodules due to incorrect insulin injection techniques are often flat and hardly visible and thus require thorough deep palpation examination and ultrasonography (US) for detection. Identifying LHs is crucial, especially in elderly and frail subjects, because they may eventually result in poor diabetes control due to associated unpredictable insulin release patterns. Raising awareness of the adequate detection of LHs and their clinical consequences is crucial and urgent. A call to action is required on this topic at all levels of undergraduate and postgraduate education.

Identifying type 1 and 2 diabetes in research datasets where classification biomarkers are unavailable: assessing the accuracy of published approaches

ObjectivesWe aimed to compare the performance of approaches for classifying insulin-treated diabetes within research datasets without measured classification biomarkers, evaluated against two independent biological definitions of diabetes type. Study Design and SettingWe compared accuracy of ten reported approaches for classifying insulin-treated diabetes into type 1 (T1D) and type 2 (T2D) diabetes in two cohorts: UK Biobank (UKBB) n = 26,399 and Diabetes Alliance for Research in England (DARE) n = 1,296. The overall performance for classifying T1D and T2D was assessed using: a T1D genetic risk score and genetic stratification method (UKBB); C-peptide measured at >3 years diabetes duration (DARE). ResultsApproaches’ accuracy ranged from 71% to 88% (UKBB) and 68% to 88% (DARE). When classifying all participants, combining early insulin requirement with a T1D probability model (incorporating diagnosis age and body image issue [BMI]), and interview-reported diabetes type (UKBB available in only 15%) consistently achieved high accuracy (UKBB 87% and 87% and DARE 85% and 88%, respectively). For identifying T1D with minimal misclassification, models with high thresholds or young diagnosis age (<20 years) had highest performance. Findings were incorporated into an online tool identifying optimum approaches based on variable availability. ConclusionModels combining continuous features with early insulin requirement are the most accurate methods for classifying insulin-treated diabetes in research datasets without measured classification biomarkers.

Stroke in patients with heart failure and reduced ejection fraction without atrial fibrillation: external validation of a risk model

Abstract Background Heart failure (HF) ranks only second to atrial fibrillation (AF) as a cause of cardio-embolic stroke. Although anticoagulation reduces this risk in HF patients not in AF, the risk/benefit profile in relatively unselected populations is not favourable. Identification of patients at high risk of stroke may allow targeted and safer use of prophylactic anticoagulant therapy. Previously, we proposed a simple risk model for stroke in patients with HF and reduced ejection fraction (HFrEF). However, this model was derived from the two older trials (published in 2007/2008) and was not externally validated. Purpose We aimed to evaluate the current incidence of stroke in patients with HFrEF not in AF receiving modern pharmacological therapy and to validate our stroke prediction model. Methods We examined patient-level data from the PARADIGM-HF, ATMOSPHERE, and DAPA-HF trials. The risk score was calculated following: 7.39×(insulin-treated diabetes) + 6.53×(previous stroke) + 2.80×[ln(NT-proBNP (pg/ml)) × 0.1182]). According to the tertile of risk score, we divided the patients into three groups. Patients with AF were defined as those with either AF on an ECG or a history of AF. Results Of the total of 20,159 patients (who experienced 590 strokes) enrolled in the three trials, 12,751 patients did not have AF at baseline. Of those, 1,143 patients (9%) had insulin-treated diabetes, 873 patients (6.8%) had a history of the previous stroke, and the median value of NT-proBNP was 1,243 pg/ml. During a median follow-up of 2.0 years, 346 (2.7%) experienced a stroke (11.7 per 1000 patient-years). Figure 1 shows cumulative incidence function plots for stroke according to the tertile of risk score in 12,331 patients whose risk score can be calculated. The number of strokes in tertile 1, 2 and 3 were 80, 102 and 149, respectively. The 3-year cumulative incidence function rates of stroke were 2.0 (95% CI: 1.5–2.5) % in tertile 1, 2.6 (95% CI: 2.1–3.2) % in tertile 2, and 4.3 (95% CI: 3.6–5.2) % in tertile 3, respectively. In patients with tertile 3, the stroke rate was 18.1 per 1000 patient-years (compared to 20.1 per 1000 patient-years in patients with AF not receiving anticoagulation). In the Cox model, risk for stroke increased according to the elevation in the risk score (tertile 2: HR 1.47 (95% CI 1.09–1.97), tertile 3: HR 2.53 (95% CI 1.92–3.33), with tertile 1 as reference). Figure 2 shows calibration plots by comparing observed and predicted probabilities of stroke at 1 to 3 years. Discrimination evaluated using the overall c-index 0.84 (95% CI: 0.75–0.91) was good. Conclusions These findings validate a previously described predictive model and confirm that it is possible to identify a subset of HFrEF patients without AF who have a risk of stroke that approximates to that in patients with AF. In these patients, the risk/benefit balance might justify the use of prophylactic anticoagulation, but this hypothesis needs to be tested prospectively. Funding Acknowledgement Type of funding sources: Foundation.

Predicting stroke in heart failure and reduced ejection fraction without atrial fibrillation.

Patients with heart failure with reduced ejection fraction (HFrEF) are at significant risk of stroke. Anticoagulation reduces this risk in patients with and without atrial fibrillation (AF), but the risk-to-benefit balance in the latter group, overall, is not favourable. Identification of patients with HFrEF, without AF, at the highest risk of stroke may allow targeted and safer use of prophylactic anticoagulant therapy. In a pooled patient-level cohort of the PARADIGM-HF, ATMOSPHERE, and DAPA-HF trials, a previously derived simple risk model for stroke, consisting of three variables (history of prior stroke, insulin-treated diabetes, and plasma N-terminal pro-B-type natriuretic peptide level), was validated. Of the 20 159 patients included, 12 751 patients did not have AF at baseline. Among patients without AF, 346 (2.7%) experienced a stroke over a median follow up of 2.0 years (rate 11.7 per 1000 patient-years). The risk for stroke increased with increasing risk score: fourth quintile hazard ratio (HR) 2.35 [95% confidence interval (CI) 1.60-3.45]; fifth quintile HR 3.73 (95% CI 2.58-5.38), with the first quintile as reference. For patients in the top quintile, the rate of stroke was 21.2 per 1000 patient-years, similar to participants with AF not receiving anticoagulation (20.1 per 1000 patient-years). Model discrimination was good with a C-index of 0.84 (0.75-0.91). It is possible to identify a subset of HFrEF patients without AF with a stroke-risk equivalent to that of patients with AF who are not anticoagulated. In these patients, the risk-to-benefit balance might justify the use of prophylactic anticoagulation, but this hypothesis needs to be tested prospectively.

Experimentally Induced Hypoglycemia-associated Autonomic Failure in Humans: Determinants, Designs, and Drawbacks.

ContextIatrogenic hypoglycemia remains one of the leading hindrances of optimal glycemic management in insulin-treated diabetes. Recurring hypoglycemia leads to a condition of hypoglycemia-associated autonomic failure (HAAF). HAAF refers to a combination of (i) impaired hormonal counterregulatory responses and (ii) hypoglycemia unawareness to subsequent hypoglycemia, substantially increasing the risk of severe hypoglycemia. Several studies since the 1990s have experimentally induced HAAF, yielding variable results.ObjectiveThe aim of this review was to assess the varying designs, clinical outcomes, potential assets, and drawbacks related to these studies.MethodA systemic literature search was conducted on PubMed and Embase in winter 2021 to include all human studies attempting to experimentally induce HAAF. In different combinations, the search terms used were “hypoglycemia-associated autonomic failure,” “HAAF,” “hypoglycemia,” “recurring,” “recurrent,” “repeated,” “consecutive,” and “unawareness,” yielding 1565 publications. Inclusion criteria were studies that had aimed at experimentally inducing HAAF and measuring outcomes of hormonal counterregulation and awareness of hypoglycemia.ResultsThe literature search yielded 27 eligible publications, of which 20 were successful in inducing HAAF while statistical significantly impairing both hormonal counterregulation and impairing awareness of hypoglycemia to subsequent hypoglycemia. Several factors were of significance as regards inducing HAAF: Foremost, the duration of antecedent hypoglycemia should be at least 90 minutes and blood glucose should be maintained below 3.4 mmol/L. Other important factors to consider are the type of participants, insulin dosage, and the risk of unintended hypoglycemia prior to the study.ConclusionHere we have outlined the most important factors to take into consideration when designing a study aimed at inducing HAAF, including to take into consideration other disease states susceptible to hypoglycemia, thus hopefully clarifying the field and allowing qualified studies in the future.

Medical Certification of Pilots Through the Insulin-Treated Diabetes Mellitus Protocol at the FAA.

INTRODUCTION: In 2019, the Federal Aviation Administration (FAA) announced a protocol to evaluate pilots with insulin treated diabetes mellitus (ITDM) for special issuance (SI) medical certification for first-/second-class pilots. The protocol's aim is improved assessment of ITDM control/hypoglycemia risk and relies on continuous glucose monitoring (CGM) data. This study compares the characteristics of first-/second-class pilots with ITDM and certification outcome.METHODS: Data was collected retrospectively from the FAA Document Imaging Workflow System (DIWS) for pilots considered for a first-/second-class SI under the ITDM program between November 2019 and October 2021. Inclusion criteria required submission of information required for certification decision (SI vs. denial). We extracted data on demographics and CGM parameters including mean glucose, standard deviation, coefficient of variance, time in range (%), time > 250 mg · dl-1 (%), and time < 70-80 mg · dl-1 (%). We compared these parameters between pilots issued an SI vs. denial with Mann-Whitney U-tests and Fisher exact tests using R.RESULTS: Of 200 pilots with ITDM identified, 77 met inclusion criteria. Of those, 55 received SIs and 22 were denied. Pilots issued SI were statistically significantly older (46 vs. 27 yr), had a lower hemoglobin A1c (6.50% vs. 7.10%), lower average glucose (139 mg · dl-1 vs. 156 mg · dl-1), and spent less time with low glucose levels (0.95% vs. 2.0%).DISCUSSION: The FAA program has successfully medically certificated pilots with ITDM for first-/second-class. Pilots granted an ITDM SI reflect significantly better diabetes control, including less potential for hypoglycemia. As this program continues, it will potentially allow previously disqualified pilots to fly safely.Stanwyck LK, DeVoll JR, Pastore J, Gamble Z, Poe A, Gui GV. Medical certification of pilots through the insulin-treated diabetes mellitus protocol at the FAA. Aerosp Med Hum Perform. 2022; 93(8):627-632.

Biomarker-driven prognostic models in chronic heart failure with preserved ejection fraction: the EMPEROR-Preserved trial.

Biomarker-driven prognostic models incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) in heart failure (HF) with preserved ejection fraction (HFpEF) are lacking. We aimed to generate a biomarker-driven prognostic tool for patients with chronic HFpEF enrolled in EMPEROR-Preserved. Multivariable Cox regression models were created for (i) the primary composite outcome of HF hospitalization or cardiovascular death, (ii) all-cause death, (iii) cardiovascular death, and (iv) HF hospitalization. PARAGON-HF was used as a validation cohort. NT-proBNP and hs-cTnT were the dominant predictors of the primary outcome, and in addition, a shorter time since last hospitalization, New York Heart Association (NYHA) class III or IV, history of chronic obstructive pulmonary disease (COPD), insulin-treated diabetes, low haemoglobin, and a longer time since HF diagnosis were key predictors (eight variables, all p< 0.001). The consequent primary outcome risk score discriminated well (c-statistic=0.75) with patients in the top 10th of risk having an event rate >22× higher than those in the bottom 10th. A model for HF hospitalization alone had even better discrimination (c= 0.79). Empagliflozin reduced the risk of cardiovascular death or hospitalization for HF in patients across all risk levels. NT-proBNP and hs-cTnT were also the dominant predictors of all-cause and cardiovascular mortality followed by history of COPD, low albumin, older age, left ventricular ejection fraction ≥50%, NYHA class III or IV and insulin-treated diabetes (eight variables, all p< 0.001). The mortality risk model had similar discrimination for all-cause and cardiovascular mortality (c-statistic=0.72 for both). External validation provided c-statistics of 0.71, 0.71, 0.72, and 0.72 for the primary outcome, HF hospitalization alone, all-cause death, and cardiovascular death, respectively. The combination of NT-proBNP and hs-cTnT along with a few readily available clinical variables provides effective risk discrimination both for morbidity and mortality in patients with HFpEF. A predictive tool-kit facilitates the ready implementation of these risk models in routine clinical practice.

Polypharmacy in diabetes: A nation-wide, pharmacy-based, observational study

AimThe aim of the present study was to build a classification of diabetes according to the time-sequence of treatment. A second aim was to describe the diversity of drugs prescribed for diabetes and associated conditions in a nation-wide cohort of patients with diabetes. Patients and methodLRx is an outpatient care nation-wide medication dispense database. It consists of a panel of 10,000 retail pharmacies in France. We developed an algorithm to find out the number of patients treated for diabetes from July 2018 to June 2019 and to classify diabetes types and the sequence of drugs dispense over the years, including treatments for the control of diabetes itself and drugs for associated conditions. ResultsA raw number of 2.3 million patients was studied, corresponding to an extrapolated 3.9 million patients in mainland France. Seven percent were classified as having Type 1 Diabetes, 86% Type 2 Diabetes (T2D), 0.5% insulin-treated gestational diabetes, and 6% remained unclassified. In subjects with T2D, metformin was the most frequently prescribed glucose lowering drug, followed by DPP4 inhibitors and sulfonylureas. Main coprescribed medication classes were lipid-modifying agents and antihypertensive agents. Of note, about a third of the patients received neuropsychiatric drugs and 40% a proton-pump inhibitor. We also had an unbiased view of compliance to treatment, that was below 50%. ConclusionThe algorithm we built could be used to monitor changes of strategies to control blood glucose and comorbidities. Our findings highlight the burden of polypharmacy in patients with diabetes.

Real-world Benefits of Diabetes Management App Use and Self-monitoring of Blood Glucose on Glycemic Control: Retrospective Analyses.

BackgroundAmong self-care measures, the self-monitoring of blood glucose (SMBG) is a critical component for checking blood glucose levels. In addition, there is growing evidence suggesting that digital technologies are being adopted as an additional method for health care systems to increase patient contact. However, for patients with non–insulin-treated diabetes mellitus type 2 (DMT2), the value of SMBG was inconsistent among studies, and the evidence for digital technologies from real-world clinical practice is still limited.ObjectiveOur study aimed to assess patients with non–insulin-treated DMT2 who were receiving care from a single clinic and analyze whether the use of a diabetes management app and SMBG behavior would affect glycemic control in a real-world clinical setting.MethodsWe collaborated with a large clinic focused on diabetes care in Taiwan that had been using the Health2Sync mobile app and web-based Patient Management Platform to collect the data. The patients were divided into 2 groups (app-engaged-user group and only-data-uploader group) according to different activities in the app, and blood glucose was recorded every month from 1 to 6 months after registration in the app. A sample of 420 patients was included in the analysis, and a linear mixed model was built to investigate which factors affected the patients’ blood glucose percentage change.ResultsUsing the mixed model coefficient estimates, we found that the percentage change was significantly negative when the only-data-uploader group was set as the baseline (t=–3.873, df=1.81 × 104; P<.001 for the patients of the app-engaged-user group). We found that for patients with shorter diabetes duration, their blood glucose decreased more than patients with longer diabetes duration (t=2.823, df=1.71 × 104; P=.005 for the number of years of diabetes duration). In addition, we found that for younger patients, their blood glucose decreased more than older patients (t=2.652, df=1.71 × 104; P=.008 for the age of the patients). Furthermore, the patients with an education level of junior high school or lower saw a significantly greater decrease in blood glucose percentage change than the patients with an education level of senior high school or higher (t=4.996, df=1.72 × 104; P<.001 for the patients with an education level of senior high school or higher). We also found that the count of blood glucose measured enlarged the decrease along the interaction months (t=–8.266, df=1.97 × 104; P<.001 for the nth month × the count of blood glucose in the nth month). Lastly, the gender of the patients did not significantly affect the percentage change (t=0.534, df=1.74 × 104; P=.59 for female patients).ConclusionsOur analysis showed the following: the blood glucose percentage change of the patients in the app-engaged-user group dropped more than that in the only-data-uploader group; shorter diabetes duration is associated with a steeper decrease in the patients’ blood glucose percentage change; the percentage decrease in blood glucose change in younger patients is greater than older patients; the blood glucose percentage change of the patients with an education level of junior high school or lower dropped more than those with an education level of senior high school or higher; and the more frequently the patients test SMBG each month, the greater the decrease in the patients’ blood glucose percentage. Further studies can be performed to consider the differences in daily behaviors such as exercise and diet across the patients and whether these factors could have vital effects on glycemic control.

681-P: Evaluation of Data Processing Performance for Subcutaneous Glucose Monitoring with an Optical Investigational Device

Background and Aims: Lumee Glucose is a small soft glucose-sensitive hydrogel (5.0 x 0.75 x 0.65mm hydrated) currently in clinical development and intended for permanent subcutaneous placement by injection to continuously monitor glucose. The sensor is comprised of a hydrogel scaffold containing fluorescent molecules that produce near infrared light proportional to glucose concentration when interrogated by an optical skin reader placed over the hydrogel. The reader utilizes a set of LEDs to excite the fluorophores within the hydrogel and communicates wirelessly with a tablet. Machine learning and quality data processing algorithms are also being assessed to establish monitoring accuracy using MARD. Methods: Glucose monitoring including a carbohydrate-rich meal was conducted during 8-hour in-clinic visits in 28 subjects with insulin-treated diabetes (female, 48 yrs [20-82], BMI 26.2kg/m2 [19.7-40.3]) over a 3-month period. Frequent venous blood glucose measurements were obtained as reference (Super GL analyzer) . Sensor signals from a total of 188 monitoring traces and 3030 paired values were subjected to retrospective data processing with 3-point glucose reference calibration using machine learning and quality filters to remove potentially compromised optical signals. Results: The average MARD for all 3030 paired values during the 6 to 91-day monitoring period was 12.3%. The MARD was 11.8% when applying additional signal quality filters. Conclusions: Following injection, the hydrogel is suitable for long-term non-invasive glucose monitoring for a minimum period of three months. Projected performance parameters are within the range of currently available glucose monitoring devices. Quality signal processing algorithms revealed marginal performance improvements and should be further optimized with respect to compensating for signal perturbations resulting from motion, temperature, and ambient light changes. Disclosure J.K.Mader: Advisory Panel; Abbott Diabetes, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis Deutschland GmbH, Speaker’s Bureau; Abbott Diabetes, Eli Lilly and Company, Medtronic, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis Deutschland GmbH, Servier Laboratories, Stock/Shareholder; decide Clinical Software GmbH. K.Rebrin: Stock/Shareholder; Profusa, Inc. R.Siegl: None. A.K.Reinhard: None. J.Kopanz: None. A.Simic: None. M.Hartmann: None. S.J.Gamsey: None. S.Banerjee: None. U.Kamecke: Consultant; Profusa, Inc.