Insulin-treated Diabetes Mellitus Research Articles

Characterization of human placental fetal vessels in gestational diabetes mellitus.

Gestational diabetes mellitus is one of the most common complications during pregnancy. Its prevalence is rapidly increasing worldwide. Gestational diabetes mellitus is leading to an elevated risk for the development of endothelial dysfunction and cardiovascular diseases both in the mother and the child in later life. The underlying pathophysiological mechanisms are not well-understood. Therefore, we aimed to characterize the endothelial function in fetal placental vessels from mothers with gestational diabetes mellitus. In this study, we distinguished between insulin-treated and diet-controlled gestational diabetes mothers and compared them to a normoglycemic control group. The clinical data confirmed pre-conceptional overweight as a risk factor in women with insulin-treated gestational diabetes mellitus. The insulin-treated gestational diabetes group was also characterized by a recent family history of diabetes compared to mothers of the control or diet-controlled gestational diabetes group. Analyses of blood serum from umbilical cords suggested a reduced fetal insulin metabolism in the insulin-treated gestational diabetes group. Vascular function analysis in fetal placental vessels revealed an altered substance P-induced vasorelaxation in vessels from patients with insulin-dependent gestational diabetes. Inhibition of nitric oxide synthase affected only fetal vessel segments from the control group or diet-controlled gestational diabetes group, but not from insulin-dependent gestational diabetes. Finally, we found a significantly decreased substance P receptor (TACR1) mRNA expression in fetal vessel segments from patients with insulin-treated gestational diabetes. In conclusion, we provide evidence that different pathophysiological mechanisms might be responsible for the development of insulin-treated versus diet-controlled gestational diabetes. Only in fetal vessels from patients with insulin-treated gestational diabetes were we able to detect an endothelial dysfunction and a reduced fetal insulin conversion. This provides novel insights into the pathophysiology of the subtypes of gestational diabetes.

Long-term clinical outcomes of drug-coated balloon angioplasty for de novo coronary lesions in patients with diabetes mellitus.

We investigated whether drug-coated balloon (DCB) treatment is effective for all de novo cases of coronary artery disease (CAD) in patients with diabetes mellitus. Furthermore, we also investigated the relationship between the degree of diabetes mellitus and clinical outcomes after DCB treatment. In this study, we included 516 consecutive patients with de novo CAD who were treated with DCB. The patients were divided into the diabetic and non-diabetic groups. Patients with diabetes mellitus were further classified into non-insulin-treated diabetes mellitus (NITDM) and insulin-treated diabetes mellitus (ITDM). The primary endpoints were major adverse cardiovascular ischemic events (MACE) and clinically driven target lesion revascularization (CD-TLR). Within a mean clinical follow-up period of 2.5years, the incidence of MACE among patients with diabetes mellitus (22.1%) was almost twice that of non-diabetic patients (11.9%) with a relative risk of 1.86 (95% CI 1.24-2.79, p = 0.002). The 3-year CD-TLR occurred in 28 patients with diabetes mellitus (10.6%) and 13 non-diabetic patients (5.1%, p = 0.02). ITDM patients had a significantly higher rate of MACE compared with non-diabetic patients with a relative risk of 2.86 (95% CI 1.76-4.63, p = 0.0002). ITDM remained an independent predictor of 3-year MACE with an odd ratio of 1.96 (95% CI 1.00-3.83, p = 0.05). In patients undergoing DCB, the presence of DM was associated with a higher risk of MACE and CD-TLR. Particularly in DCB, treatment was still inadequately effective for ITDM patients.

Significance of diabetes mellitus status in patients undergoing percutaneous left main coronary artery intervention.

Diabetes mellitus (DM) is a modifiable risk factor for patients with coronary artery disease (CAD). Treatment with insulin correlates with advanced disease and has been associated with excess cardiovascular risk, but evidence on outcomes of patients with insulin-treated DM (ITDM) undergoing left main percutaneous coronary intervention (LMPCI) remains scarce. The aim of the presented study is to evluate the risk attributable to DM and ITDM in patients undergoing LMPCI. We included 869 patients undergoing PCI for unprotected LMCAD. The cohort was divided into three subgroups based on diabetic status: No DM, ITDM, and Non-ITDM. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of death, spontaneous myocardial infarction (MI), or stroke at 1 year. Results were adjusted for clinically relevant baseline characteristics. Amongst participants, 58.7% had no DM, 25.9% non-ITDM, and 15.4% ITDM. Diabetics were younger and more likely to be female. They also exhibited higher body mass index as well as prevalence of comorbidities, including hypertension, anemia, and chronic kidney disease. The number of bifurcation lesions and stents used was similar between groups. At 1 year, when compared to no DM, ITDM (25.4% vs. 10.0%, p < 0.01) but not non-ITDM (10.8% vs. 10.0%, p = 0.94) demonstrated higher MACCE. This finding was driven by increased risk of MI. Mortality was 8.4%, 7.8%, and 17.2% for no DM, Non-ITDM, and ITDM, respectively. Results remained unchanged after adjustment. In a rather contemporary patient population undergoing PCI for LMCAD, ITDM but not non-ITDM was associated with higher risk of 1-year MACCE, primarily driven by MI.

Diffuse pulmonary hemorrhage as a rare presentation of pheochromocytoma: a case report with review of the literature

A 37-year-old male patient with a past history of fluctuating hypertension and insulin-treated diabetes mellitus presented to our clinic with a 1-year history of sudden-onset cough, dyspnea, and frank hemoptysis. Examination showed asthenia, moderate anemia, uncontrolled blood pressure, and a past history of one admission for management of hemoptysis and cardiac failure. The evaluation showed mild anemia, azotemia, low ejection fraction, contrast-enhanced computed tomography (CECT) of the chest, and sputum suggestive of pulmonary hemorrhage. Investigation during current admission revealed proteinuria, left suprarenal mass on USG, and clear lung parenchyma on chest X-ray and CECT. Autoimmune workup for vasculitis was negative and 24-h urinary catecholamine levels were elevated with CECT abdomen confirming pheochromocytoma. His blood pressure was controlled and he underwent laparoscopic left adrenalectomy with confirmation on histopathology. Postoperatively he is doing well with minimal requirement of antihypertensive, and diabetes is controlled with diet and exercise only. This case highlights diffuse alveolar hemorrhage as a rare presentation of pheochromocytoma. This case also highlights that secondary cause of hypertension should always be ruled out in case of uncontrolled hypertension in young patients to prevent devastating complications.

Long-term albumin improves the outcomes of patients with decompensated cirrhosis and diabetes mellitus: Post hoc analysis of the ANSWER trial.

Type-2 diabetes mellitus is a frequent comorbidity of cirrhosis independently associated with cirrhosis-related complications and mortality. This post hoc analysis of the ANSWER trial database assessed the effects of long-term human albumin (HA) administration on top of the standard medical treatment (SMT) on the clinical outcomes of a subgroup of 85 outpatients with liver cirrhosis, uncomplicated ascites and insulin-treated diabetes mellitus type 2 (ITDM). Compared to patients in the SMT arm, the SMT + HA group showed a better overall survival (86% vs. 57%, p = .016) and lower incidence rates of paracenteses, overt hepatic encephalopathy, bacterial infections, renal dysfunction and electrolyte disorders. Hospital admissions did not differ between the two arms, but the number of days spent in hospital was lower in the SMT + HA group. In conclusion, in a subgroup of ITDM outpatients with decompensated cirrhosis and ascites, long-term HA administration was associated with better survival and a lower incidence of cirrhosis-related complications.

Development of a requirement for exogenous insulin treatment in dogs with hyperglycemia.

It has been suggested that overt diabetes mellitus in dogs be defined based on a persistent fasting blood glucose concentration (BGC) >144 mg/dL. Determine the number of dogs with randomly identified hyperglycemia without insulin-treated diabetes mellitus (ITDM) that later develop a need for exogenous insulin treatment. A total of 1318 dogs examined at a university teaching hospital without ITDM and with randomly identified hyperglycemia. Retrospective longitudinal study. Hyperglycemia was defined as randomly identified BGC above >112 mg/dL, moderate hyperglycemia as BGC >144 mg/dL but <200 mg/dL and pronounced hyperglycemia as BGC ≥200 mg/dL. Dogs were defined as having ITDM if they were treated with insulin. Follow-up was attempted 7 to 12 years after hyperglycemia was documented to determine if over time dogs developed a need for exogenous insulin treatment. Twenty-nine of 824 dogs (3.5%) with hyperglycemia and follow-up information developed ITDM, including 3/824 dogs (0.4%) with moderate hyperglycemia, and 2/824 dogs (0.2%) with pronounced hyperglycemia. Most dogs with hyperglycemia that developed ITDM (24/29, 83%) had BGC ≤144 mg/dL. Among dogs that eventually developed a need for exogenous insulin treatment, no association was found between the degree of hyperglycemia and the time interval between documentation of hyperglycemia and diagnosis of ITDM. Logistic regression determined that BGC is not significantly associated with ITDM. Most dogs with randomly identified hyperglycemia did not develop a need for exogenous insulin treatment. Other criteria could be required to augment the definition of overt DM in non-insulin treated dogs.

Time-dependent progress of lower urinary tract dysfunction in streptozotocin-induced diabetic rats with or without low-dose insulin treatment.

Objectives: To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin treatment and explore the pathophysiological characteristics of insulin therapy on lower urinary tract dysfunction (LUTD) caused by diabetes mellitus (DM). Methods: Female Sprague-Dawley rats were divided into five groups: normal control (NC) group, 4 weeks insulin-treated DM (4-DI) group, 4 weeks DM (4-DM) group, 8 weeks insulin-treated DM (8-DI) group and 8 weeks DM (8-DM) group. DM was initially induced by i.p. injection of streptozotocin (65 mg/kg), and then the DI groups received subcutaneous implantation of insulin pellets under the mid dorsal skin. Voiding behavior was evaluated in metabolic cages. The function of bladder and urethra in vivo were evaluated by simultaneous recordings of the cystometrogram and urethral perfusion pressure (UPP) under urethane anesthesia. The function of bladder and urethra in vitro were tested by organ bath techniques. The morphologic changes of the bladder and urethra were investigated using Hematoxylin-Eosin and Masson's staining. Results: Both 4-and 8-weeks diabetic rats have altered micturition patterns, including increased 12-h urine volume, urinary frequency/12 hours and voided volume. In-vivo urodynamics showed the EUS bursting activity duration is longer in 4-DM group and shorter in 8-DM group compared to NC group. UPP change in 8-DM were significantly lower than NC group. While none of these changes were found between DI and NC groups. Organ bath showed the response to Carbachol and EFS in bladder smooth muscle per tissue weights was decreased significantly in 4- and 8-weeks DM groups compared with insulin-treated DM or NC groups. In contrast, the contraction of urethral muscle and maximum urethral muscle contraction per gram of the tissue to EFS stimulation were significantly increased in 4- and 8-weeks DM groups. The thickness of bladder smooth muscle was time-dependently increased, but the thickness of the urethral muscle had no difference. Conclusions: DM-induced LUTD is characterized by time-dependent functional and structural remodeling in the bladder and urethra, which shows the hypertrophy of the bladder smooth muscle, reduced urethral smooth muscle relaxation and EUS dysfunction. Low-dose insulin can protect against diuresis-induced bladder over-distention, preserve urethral relaxation and protect EUS bursting activity, which would be helpful to study the slow-onset, time-dependent progress of DM-induced LUTD.

Does insulin therapy affect all-cause mortality? machine learning complements propensity score analysis in a pharmacoepidemiologic study of adult diabetic females in Barranquilla, Colombia

Aims: To investigate all-cause mortality (ACM) attributable to insulin treated diabetes mellitus through propensity score (PS)-weighting with and without novel confounders identified by Random Survival Forest (a machine learning approach). Methods: Prospective clinic encounter data was obtained from 1517 females with Type 2 diabetes (mean age 63±12 years) from Barranquilla, Colombia (2003 – 2016, censored August 2017) for a median 10-year mortality follow-up. Risk variables of importance for ACM were identified on RSF screening. Survival was compared in retrospective cohorts, identified by baseline treatment with glucose-lowering therapy, and balanced for confounders through PS-weighting with and without RSF variables using multivariable Cox regression. Results: RSF screening identified new risk variables (e.g., recruitment year, parity, reproductive lifespan) for ACM in women receiving insulin. The unweighted risk estimate showed a nonsignificant increased risk for ACM [HR 1.32 (.9, 2), p=0.2] compared to noninsulin treated women. After balancing for risk covariates in the compared cohorts, PS showed no significant effect of insulin on all-cause mortality [HR 95% CI 0.83 (0.5, 1.4) p=0.5] whereas PS-weighted analyses incorporating RSF novel variables approached conservative ACM estimates [HR 95% CI 0.56 (0.3, 1.0) p=0.07)]. The estimated ACM risk from active smoking was also more conservative with RSF weighting. Conclusion: In this observational study, insulin treatment appeared to be a surrogate for higher-risk women with diabetes mellitus. RSF-augmented PS analysis showed that insulin treatment may potentially be associated with a survival advantage compared to non-insulin treatment in older female diabetics.

Influence of sex on the functional assessment of myocardial ischemia.

Fractional flow reserve (FFR) and non-hyperemic resting pressure ratios, such as instantaneous wave-free ratio (iFR) and resting full-cycle ratio (RFR), are recommended for evaluating the significance of angiographically intermediate coronary stenoses. Despite their usefulness, approximately 20% of assessed lesions exhibit discordance between FFR and iFR/RFR. The role of sex in this discrepancy remains uncertain; thus, we aimed to investigate its impact on the discordance between FFR and iFR/RFR. We reviewed 417 consecutive intermediate stenotic lesions from 381 patients, stratified by sex and assessed with both FFR and iFR/RFR. FFR≤0.80 and iFR/RFR ≤0.89 were considered positive for ischemia. Among the 381 patients, 92 (24.1%) were women. Women were older, had lower estimated glomerular filtration rate (eGFR), a higher ejection fraction, and were more likely to have peripheral artery disease than men. Median FFR and iFR/RFR values were lower in men than in women (FFR 0.86 vs. 0.80; P < 0.001; iFR 0.92 vs. 0.90; P = 0.049). However, overall discordance prevalence was similar for both sexes (20.6% vs. 15.1%; P = 0.22). In men, eGFR, insulin-treated diabetes mellitus, and arterial hypertension were predictors of positive FFR | negative iFR/RFR discordance, while eGFR, insulin-treated diabetes mellitus, atrial fibrillation, and chronic obstructive pulmonary disease were predictors of negative FFR | positive iFR/RFR discordance. No factors associated with either discordance were identified in women. FFR and iFR/RFR results indicating significant ischemia were more common in men than women when assessing intermediate coronary stenoses. Nevertheless, sex did not predict discordant results.

Continuous glucose monitoring metrics and pregnancy outcomes in insulin-treated diabetes: A post-hoc analysis of the GlucoMOMS trial.

To investigate the association between continuous glucose monitoring (CGM) metrics and perinatal outcomes in insulin-treated diabetes mellitus in pregnancy. In a post-hoc analysis of the GlucoMOMS randomized controlled trial, we investigated the association between the metrics of an offline, intermittent CGM, glycated haemoglobin (HbA1c) and perinatal outcomes per trimester in different types of diabetes (type 1, 2 or insulin-treated gestational diabetes mellitus [GDM]). Data were analysed using multivariable binary logistic regression. Outcomes of interest were neonatal hypoglycaemia, pre-eclampsia, preterm birth, large for gestational age (LGA) and Neonatal Intensive Care Unit (NICU) admission. The glucose target range was defined as 3.5-7.8 mmol/L (63-140 mg/dL). Of the 147 participants (N = 50 type 1 diabetes, N = 94 type 2 diabetes/insulin-treated GDM) randomized to the CGM group of the GlucoMOMS trial, 115 participants had CGM metrics available and were included in the current study. We found that, in pregnancies with type 1 diabetes, a higher second trimester mean glucose was associated with LGA (odds ratio 2.6 [95% confidence interval 1.1-6.2]). In type 2 and insulin-treated gestational diabetes, an increased area under the curve above limit was associated with LGA (odds ratio 10.0 [95% confidence interval 1.4-72.8]). None of the CGM metrics were associated with neonatal hypoglycaemia, pre-eclampsia, shoulder dystocia, preterm birth and NICU admission rates for pregnancies complicated by any type of diabetes. In this study, in type 2 diabetes or insulin-treated GDM, the glucose increased area under the curve above limit was associated with increased LGA. In type 1 diabetes, the mean glucose was the major determinant of LGA. Our study found no evidence that other CGM metrics determined adverse pregnancy outcomes.

1047-P: Evaluating Discharge Prescription Errors and the Clinical Impacts in Patients with Insulin-Treated Diabetes Mellitus in a Community Hospital

Introduction: Transitioning patients with insulin treated diabetes (ITDM) at time of hospital discharge is identified as a source of error in how information for home management is provided that can contribute to significant adverse health outcomes. To address this, we conducted a quality improvement project investigating the safety of current discharge procedures in our hospital and the impact on glycemic control at 3 months and diabetes related readmissions at 3 and 6 months. Methods: We retrospectively analyzed discharge prescription errors in patients with ITDM in a community hospital between January 2020 and December 2021. Errors were defined as being discharged on the wrong form of insulin (pen vs vial), and/or not being provided appropriate insulin administration devices (i.e., pen needles or syringes). Data was collected by reviewing discharge summaries, discharge medication reconciliations and pharmacy records. Results: Among 75 patients with ITDM (62 (82%) T2DM, 12 (16%) T1DM, 1 (1%) ketosis-prone DM), errors were noted in 73 (97%) patients. 46 (63%) were discharged on wrong form of insulin and 67 (91%) were discharged without appropriate insulin administration devices. Among those 73 patients, 19 (26%) patients had an increase in HbA1c at 3 months (8.7 vs 10.03, p=0.001); 5 (25%) and 8 (24%) had 30-day and 90-day diabetes-related hospital readmissions, respectively. In 2 patients with appropriate discharge, there were no 30-day or 90-day hospital readmissions. Conclusion: Prescription errors in patients with ITDM at discharge are common and potentially remediable and lead to hospital readmissions and poor glycemic control. These results demonstrate the need for increased awareness among providers through adoption of standardized discharge insulin order sets in EMR system including the form of insulin, insulin administration devices and supplies as well as for early post-discharge follow up with endocrinology. Disclosure A.N.Keskinkilic: None. M.T.Korytkowski: None. S.Mon: None.

Influence of diabetes mellitus on the invasive assessment of myocardial ischemia in patients with coronary artery disease.

Current guidelines recommend physiological evaluation of borderline coronary artery stenoses using hyperemic (fractional flow reserve [FFR]) and nonhyperemic (instantaneous wave‑free ratio [iFR] and resting full‑cycle ratio [RFR]) methods. However, comorbidities, such as diabetes mellitus (DM), may influence the results of the assessment. We sought to investigate the impact of DM and insulin treatment on the discordance between FFR and iFR/RFR. A total of 417 intermediate stenoses in 381 patients underwent FFR and iFR/RFR assessment. FFR lower than or equal to 0.8 and iFR/RFR lower than or equal to 0.89 indicated significant ischemia. The patients were categorized based on DM diagnosis and insulin treatment status. Of the 381 patients, 154 (40.4%) had DM. Among these, 58 patients (37.7%) received insulin treatment. Diabetic patients had higher body mass index and glycated hemoglobin levels, and lower ejection fraction. FFR and iFR/RFR analyses were conducted in 417 vessels with available measurements for both tests. A good correlation between FFR and iFR/RFR was confirmed in both diabetic (R = 0.77) and nondiabetic (R = 0.74) patients. Discordance between FFR and iFR/RFR occurred in approximately 20% of cases, and the frequency of discordance was not affected by the diabetic status. However, insulin‑treated DM was independently associated with a higher risk of negative FFR and positive iFR/RFR discordance (odds ratio, 4.61; 95% CI, 1.38-15.4; P = 0.01). Also, the optimal cutoff value for FFR identifying significant ischemia in DM patients treated with insulin was higher (0.84) than the generally recommended value. The rate of FFR and iFR/FFR discordance was similar regardless of the diabetes status, and insulin‑treated DM was associated with an increased risk of negative FFR and positive iFR/RFR discordance.

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.

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.

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.

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.

Clinical outcomes in patients with atrial fibrillation with or without concomitant diabetes after two years of edoxaban treatment: ETNA-AF-Europe registry

Abstract Background/Introduction Concomitant diabetes mellitus (DM) in patients with atrial fibrillation (AF) has been associated with a higher risk of stroke/systemic embolic events (SEE), and higher mortality. Purpose To evaluate effectiveness and safety outcomes in AF patients with different types of concomitant DM vs those without concomitant DM after 2 years of edoxaban treatment in a sub-analysis of the prospective ETNA-AF-Europe registry. Methods Patients with AF who received edoxaban once daily were enrolled across 825 centres in 10 European countries. This sub-analysis is based on a data snapshot from 26th October 2020. Patients were grouped by DM status (with or without DM; insulin-treated or non-insulin-treated DM). Baseline characteristics are summarised descriptively. Kaplan-Meier (KM) survival curves of outcomes were constructed; annualised event rates (AERs; %/year) and comparisons between patients with or without DM by univariate analysis are presented. Comparisons of patients with insulin- vs non-insulin-treated DM were made by multivariate analysis adjusted for HbA1c. Results Patients' demographics and baseline characteristics are shown in Table 1. Of 13,133 patients with AF, 2885 (22.0%) had DM. Among patients with DM, 2756 (95.6%) received treatment: 605 (22.0%) with insulin and 2151 (78.0%) with non-insulin treatments. KM curves for effectiveness and safety outcomes are shown in Figure 1. AERs (%/year) of ischaemic stroke/transient ischaemic attack (TIA)/SEE were 0.86% in patients with AF and no DM, 0.87% with non-insulin-treated DM (p=0.9216 vs no DM) and 1.81% with insulin-treated DM (p=0.0022 vs no DM; p=0.0014 vs non-insulin-treated DM). AERs of myocardial infarction (MI) were 0.40%, 0.43% (p=0.7454 vs no DM), and 1.04% (p=0.0033 vs no DM) respectively; of major bleeding were 0.90%, 1.10% (p=0.2427 vs no DM), and 1.71% (p=0.0106 vs no DM), respectively; and of all-cause death were 3.36%, 5.02% (p&amp;lt;0.0001 vs no DM), and 8.91% (p&amp;lt;0.0001 vs no DM) respectively. In a multivariate analysis of DM patients adjusted for HbA1c (patients with AF and DM with HbA1c measured, n=1869), patients with AF and insulin-treated DM had a higher risk of stroke/TIA/SEE (HbA1c adjusted HR [95% CI]: 2.13 [1.12–4.05], p=0.0205) and all-cause death (1.83 [1.35–2.49], p=0.0001) vs those with non-insulin-treated DM; no significant difference in the risk of MI (2.10 [0.78–5.66], p=0.1448) or major bleeding (1.81 [0.95–3.44], p=0.0706) was detected between the groups. Conclusion In patients with AF and DM, risk of stroke/TIA/SEE, MI and major bleeding was confined to insulin-treated DM patients only. These patients also had poorer survival rates vs those without DM and those with non-insulin-treated DM, reinforcing previously published data showing a strong association between insulin treatment and poorer outcomes, and a mild/absent association between non-insulin treatments and poorer outcomes in patients with AF and DM. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This research was funded by Daiichi Sankyo Europe.

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.

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.