Incidence, implications, and management of sense-B-noise failure in subcutaneous cardioverter-defibrillator patients: insights from a large multicentre registry.

AIMS: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) offer potentially distinct advantages over transvenous defibrillator systems. Recent randomized trials showed significantly lower lead failure rates than transvenous ICD. Still, S-ICDs remain associated with the risk of inappropriate shocks (IAS). While previous studies have reported varying causes of IAS, this study explores a rare cause of IAS, referred to as 'sense-B-noise.' It was recently described in case series, but its incidence has not been studied in a large cohort of S-ICD patients. METHODS AND RESULTS: We retrospectively reviewed data from patients implanted with S-ICD models 1010, A209, and A219 between October 2009 and July 2023 across nine centres in Europe and the USA. The analysis concentrated on determining the incidence and understanding the implications of sense-B-noise events. Sense-B-noise represents a rare manifestation of distinct electrogram abnormalities within the primary and alternate sensing vectors. Data were collected from medical records, device telemetry, and manufacturer reports for investigation. This registry is registered on clinicaltrials.gov (NCT05713708). Subcutaneous implantable cardioverter-defibrillator devices of the 1158 patients were analysed. The median follow-up time for all patients was 46 (IQR 23-64) months. In 107 patients (9.2%) ≥1 IAS was observed during follow-up. Sense-B-noise failure was diagnosed in six (0.5 and 5.6% of all IAS) patients, in all patients, the diagnosis was made after an IAS episode. Median lead dwell time in the affected patients was 23 (2-70) months. To resolve the sense-B-noise defect, in three patients reprogramming to the secondary vector was undertaken, and two patients underwent system removal with subsequent S-ICD reimplantation due to low amplitude in the secondary vector. In one patient, the secondary vector was initially programmed, and subsequently, an S-ICD system exchange was performed due to T-wave-oversensing IAS episodes. CONCLUSION: This multicentre analysis' findings shed light on a rare but clinically highly significant adverse event in S-ICD therapy. To our knowledge, we provide the first systematic multicentre analysis investigating the incidence of sense-B-noise. Due to being difficult to diagnose and limited options for resolution, management of sense-B-noise is challenging. Complete system exchange may be the only option for some patients. Educating healthcare providers involved in S-ICD patient care is crucial for ensuring accurate diagnosis and effective management of sense-B-noise issues.

Occurrence of Premature Battery Depletion in a Large Multicenter Registry of Subcutaneous Cardioverter-Defibrillator Patients.

AIMS AND BACKGROUND: Subcutaneous implantable cardioverter-defibrillators (S-ICD) have become established in preventing sudden cardiac death, with some advantages over transvenous defibrillator systems, including a lower incidence of lead failures. Despite technological advancements, S-ICD carriers may suffer from significant complications, such as premature battery depletion (PBD) which led to an advisory for nearly 40,000 patients. This multicenter study evaluated the incidence of PBD in a large set of S-ICD patients. METHODS: Data from patients implanted with S-ICD models A209 and A219 between October 2012 and July 2023 across 9 centers in Europe and the USA was reviewed. Incidence and implications of PBD, defined as clinically observed sudden drop in battery longevity were analyzed and compared to PBD with the definition of battery depletion within 60 months. Prospectively collected clinical data was obtained retrospectively from medical records, device telemetry, and manufacturer reports. This registry is listed on clinicaltrials.gov (NCT05713708). RESULTS: Of the 1,112 S-ICD devices analyzed, 547 (49.2%) were equipped with a potentially affected capacitor linked to PBD occurrence, currently under FDA advisory. The median follow-up time for all patients was 46 (IQR 24-63) months. Clinically suspected PBD was observed in 159 (29.1%) of cases, with a median time to generator removal or replacement of 65 (IQR 55-72) months, indicative of significant deviations from expected battery lifespan. Manufacturer confirmation of PBD was made in 91.7% of devices returned for analysis. No cases of PBD were observed in devices that were not under advisory. CONCLUSION: This manufacturer-independent analysis highlights a notable incidence of PBD in patients equipped with S-ICD models under advisory and the rate of PBD in this study corresponds to the rate currently estimated by the manufacturer. To the best of our knowledge this provides the largest contemporary peer-reviewed study cohort investigating the actual incidence of PBD in S-ICD patients. These findings emphasize the importance of post-market registries in collaboration between clinicians and the manufacturer to optimize safety and efficacy in S-ICD treatment.

Screening for diabetes distress and depression in routine clinical care for youth with type 1 diabetes.

OBJECTIVE: The purpose of this study is to examine diabetes distress as a potential mediator of the relationship between depression symptoms and diabetes outcomes, including hemoglobin A1c (hemoglobin A1c [HbA1c]) and diabetes management behaviors in a clinical sample of adolescents and young adults. METHODS: In a pediatric diabetes clinic, 716 youth (ages 12-21 years) completed measures of diabetes distress (Problem Areas in Diabetes-Teen [PAID-T]), a single-item of diabetes distress, and depression (Patient Health Questionnaire [PHQ-9]) as part of standard care. Electronic health records were extracted for the "Six Habits" and glycemic management (HbA1c). RESULTS: Overall, 3.6% (n = 26) of adolescents had clinically elevated diabetes distress and depression symptoms, 5.0% had diabetes distress alone, 8.7% had depression symptoms alone, and 82.7% had neither clinical elevation of diabetes distress nor depression symptoms. Results of mediation analysis demonstrated diabetes distress (both full and single-item measures) fully mediated the relationship between depression symptoms and HbA1c (p < .001). Also, mediation analysis results showcase incomplete mediation of the effect of the Six Habits score on HbA1c appears by PAID-T Diabetes Distress. CONCLUSIONS: In a clinical sample of youth with type 1 diabetes, both depressive symptoms and diabetes distress are associated with HbA1c. Furthermore, diabetes distress fully mediates the relationship between depressive symptoms and HbA1c. As part of standard clinical care, the single-item screener for diabetes distress captured similar results as the full-scaled PAID-T. With limited clinical resources, providers may consider focusing assessment and interventions on the psychological factor of diabetes distress within the diabetes clinic to maximize the impact on glycemic control and consider the use of single-item screening to identify distress.

Clinical Protocol for Selecting Intracardiac or Transesophageal Echocardiography-Guided Left Atrial Appendage Occlusion.

Intracardiac echocardiography (ICE) has emerged as an alternative to transesophageal echo (TEE) to guide left atrial appendage occlusion (LAAO). We established a protocol to select patients appropriate for ICE guidance. Patients who underwent LAAO with the Watchman or Watchman FLX device (Boston Scientific, Marlborough, Massachusetts) from January 2018 to March 2022 at a large United States center were included. The novel protocol prospectively selected TEE or ICE guidance beginning in January 2020; previous LAAO procedures were retrospectively included. ICE was selected for patients with uninterrupted anticoagulation and appropriate LAA anatomy, renal function, and moderate sedation tolerance. In-hospital outcomes with successful implantation without conversion to TEE guidance, no peridevice leak, and no procedural complications were compared. Composite 1-year outcome included freedom from peridevice leak, device-related thrombus, stroke, and all-cause mortality. A total of 234 patients were included; the mean age was 76.1 ± 8.3 years old, and 42.3% were female. ICE guidance was used for 63 procedures; TEE guidance was used for 171 procedures. For the composite outcome, ICE-guided LAAO was superior to TEE-guided LAAO (risk difference 0.102, 96.8% vs 86.5%, 95% confidence interval 0.003 to 0.203, p = 0.029). In comparison to the TEE-guided group, ICE-guided procedures were shorter (89.1 ± 26.3 vs 99.8 ± 30.0 min, p = 0.0087) with less general anesthesia (26.6% vs 98.8%, p <0.0001). One-year composite adverse outcomes did not differ significantly (80.7% vs 88.9%, p = 0.17). In conclusion, the protocol to select appropriate patients for ICE versus TEE guidance for LAAO is safe and effective. Larger studies are indicated to validate this approach to improve outcomes, shorten procedures, and avoid general anesthesia.

Psychosocial Care for People With Diabetic Neuropathy: Time for Action.

Psychological factors and psychosocial care for individuals with diabetic neuropathy (DN), a common and burdensome complication of diabetes, are important but overlooked areas. In this article we focus on common clinical manifestations of DN, unremitting neuropathic pain, postural instability, and foot complications, and their psychosocial impact, including depression, anxiety, poor sleep quality, and specific problems such as fear of falling and fear of amputation. We also summarize the evidence regarding the negative impact of psychological factors such as depression on DN, self-care tasks, and future health outcomes. The clinical problem of underdetection and undertreatment of psychological problems is described, together with the value of using brief assessments of these in clinical care. We conclude by discussing trial evidence regarding the effectiveness of current pharmacological and nonpharmacological approaches and also future directions for developing and testing new psychological treatments for DN and its clinical manifestations.

Cost and utilization of healthcare services for persons with diabetes.

AIMS: Describe and compare healthcare costs and utilization for insured persons with type 1 diabetes (T1D), type 2 diabetes (T2D), and without diabetes in the United States. METHODS: Using a nationally representative healthcare claims database, we identified matched persons with T1D, T2D, and without diabetes using a propensity score quasi-randomization technique. In each year between 2009 and 2018, we report costs (total and out-of-pocket) and utilization for all healthcare services and those specific to medications, diabetes-related supplies, visits to providers, hospitalizations, and emergency department visits. RESULTS: In 2018, we found out-of-pocket costs and total costs were highest for persons with T1D (out-of-pocket: $2,037.2, total: $25,652.0), followed by T2D (out-of-pocket: $1,543.3, total: $22,408.1), and without diabetes (out-of-pocket: $1,122.7, total: $14,220.6). From 2009 to 2018, out-of-pocket costs were increasing for persons with T1D(+6.5 %) but decreasing for T2D (-7.5 %) and without diabetes (-2.3 %). Medication costs made up the largest proportion of out-of-pocket costs regardless of diabetes status (T1D: 51.4 %, T2D: 55.4 %,without diabetes: 51.1 %). CONCLUSIONS: Given the substantial out-of-pocket costs for people with diabetes, especially for those with T1D, providers should screen all persons with diabetes for financial toxicity (i.e., wide-ranging problems stemming from healthcare costs). In addition, policies that aim to lower out-of-pocket costs of cost-effective diabetes related healthcare are needed with a particular focus on medications.

Prevalence and Impact of Poorly Controlled Modifiable Risk Factors Among Patients Who Underwent Atrial Fibrillation Ablation.

Managing atrial fibrillation (AF) risk factors (RFs) improves ablation outcomes in obese patients. However, real-world data, including nonobese patients, are limited. This study examined the modifiable RFs of consecutive patients who underwent AF ablation at a tertiary care hospital from 2012 to 2019. The prespecified RFs included body mass index (BMI) ≥30 kg/m2, >5% fluctuation in BMI, obstructive sleep apnea with continuous positive airway pressure noncompliance, uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, tobacco use, alcohol use higher than the standard recommendation, and a diagnosis-to-ablation time (DAT) >1.5 years. The primary outcome was a composite of arrhythmia recurrence, cardiovascular admissions, and cardiovascular death. In this study, a high prevalence of preablation modifiable RFs was observed. More than 50% of the 724 study patients had uncontrolled hyperlipidemia, a BMI ≥30 mg/m2, a fluctuating BMI >5%, or a delayed DAT. During a median follow-up of 2.6 (interquartile range 1.4 to 4.6) years, 467 patients (64.5%) met the primary outcome. Independent RFs were a fluctuation in BMI >5% (hazard ratio [HR] 1.31, p = 0.008), diabetes with A1c ≥6.5% (HR 1.50, p = 0.014), and uncontrolled hyperlipidemia (HR 1.30, p = 0.005). A total of 264 patients (36.46%) had at least 2 of these predictive RFs, which was associated with a higher incidence of the primary outcome. Delayed DAT over 1.5 years did not alter the ablation outcome. In conclusion, substantial portions of patients who underwent AF ablation have potentially modifiable RFs that were not well controlled. Fluctuating BMI, diabetes with hemoglobin A1c ≥6.5%, and uncontrolled hyperlipidemia portend an increased risk of recurrent arrhythmia, cardiovascular hospitalizations, and mortality after ablation.

Clinician Experiences With Hybrid Closed Loop Insulin Delivery Systems in Veterans With Type 1 Diabetes: Qualitative Study.

BACKGROUND: Hybrid closed loop (HCL) insulin pumps adjust insulin delivery based on input from a continuous glucose monitor. Several systems are FDA approved and associated with improved time in range, reduction in hemoglobin A1c, and decreased incidence of hypoglycemia. Major diabetes guidelines differ in their strength of recommendations regarding the use of HCL systems. Overall, limited information about the factors that influence HCL pump clinical decision-making is available, especially among endocrinology clinicians. OBJECTIVE: The study objective is to describe the knowledge and attitudes, network support, and self-efficacy regarding HCL insulin delivery systems among endocrinology clinicians in one Veterans Affairs (VA) Healthcare System in the Midwest. METHODS: Following a descriptive approach, this qualitative study used semistructured interviews and inductive thematic analysis. All endocrinologists, endocrinology fellows, and nurses in the endocrinology and metabolism department at one VA Healthcare System in the Midwest were invited to participate in one-on-one phone interviews. Thematic analysis explored clinician perspectives on HCL insulin pump systems. RESULTS: Participants (n=11) had experience within VA and university health care system endocrinology clinics. From their experiences, 4 themes were identified involving the evaluation and assessment of insulin pump candidates, prescribing challenges, clinical benefits of HCL pumps, and overall clinician confidence. CONCLUSIONS: Findings suggest that clinicians believe HCL systems have significant glycemic benefits but are not appropriate for all patients, especially those with cognitive impairment. HCL pump initiation is a multi-step process requiring an interdisciplinary team of health care clinicians to ensure patient and pump success. Furthermore, HCL systems improve clinician confidence in overall diabetes management.

Predictive value of interatrial block on electrocardiogram among obese patients undergoing atrial fibrillation ablation.

BACKGROUND: Determine a predictive value of interatrial block (IAB) on atrial fibrillation (AF) ablation outcomes in obese patients. METHODS: Medical records were retrospectively reviewed for 205 consecutive patients with body mass indices (BMI) ≥ 30 kg/m2 who underwent initial AF ablation. Evidence of partial IAB defined as P-wave duration (PWD) ≥ 120 ms and advanced IAB with PWD ≥ 120 ms and biphasic or negative P-wave in inferior leads was examined from sinus electrocardiograms (ECGs) within 1-year pre-ablation. The primary outcome was recurrent atrial arrhythmia after 3-month blanking period post-ablation. RESULTS: The mean BMI was 36.9 ± 5.7 kg/m2. Partial IAB and advanced IAB were observed in 155 (75.61%) and 42 (20.49%) patients, respectively. During the median follow-up of 1.35 (interquartile range 0.74, 2.74) years, 115 (56.1%) patients had recurrent atrial arrhythmias. In multivariable analysis adjusting for age, gender, persistent AF, use of antiarrhythmic drugs (AADs), left atrial volume index (LAVI), partial IAB, and advanced IAB were independent predictors of recurrent arrhythmia with hazard ratio (HR) of 2.80 (95% confidence interval [CI] 1.47-6.05; p = 0.001) and HR 1.79 (95% CI 1.11-2.82; p = 0.017), respectively. The results were similar in a subgroup analysis of patients who had no severe left atrial enlargement and a subgroup analysis of patients who were not on AADs. CONCLUSIONS: IAB is highly prevalent in patients with obesity and AF. Partial IAB, defined as PWD ≥ 120 ms, and advanced IAB with evidence of biphasic P-wave in inferior leads were independently associated with increased risk of recurrent arrhythmia after AF ablation. Its predictive value is independent of other traditional risk factors, LAVI, or use of AADs.

The conundrum of diabetic neuropathies-Past, present, and future.

Diabetic neuropathy (DN) remains arguably the most prevalent chronic complication in people with both type 1 and type 2 diabetes, including in youth, despite changes in the current standards of clinical care. Additionally, emerging evidence demonstrates that neuropathy affects a large proportion of people with undiagnosed diabetes and/or prediabetes, as well as those with obesity. Here we summarize the latest epidemiology of DN, recent findings regarding the pathophysiology of the disease, as well as current outcome measures for screening and diagnosis, in research and clinical settings. The authors discuss novel perspectives on the impact of social determinants of health in DN development and management, and the latest evidence on effective therapies, including pharmacological and nonpharmacological therapies for neuropathic pain. Throughout the publication, we identify knowledge gaps and the need for future funding to address these gaps, as well as needs to advocate for a personalized care approach to reduce the burden of DN and optimize quality of life for all affected individuals.

Symptomatic diabetic autonomic neuropathy in type 1 diabetes (T1D): Findings from the T1D exchange.

AIMS: We aimed to evaluate the contemporary prevalence of and risk factors for symptomatic diabetic autonomic neuropathy (DAN) in participants with type 1 diabetes (T1D) enrolled in the T1D Exchange Clinic Registry. METHODS: DAN symptoms and severity were assessed with the Survey of Autonomic Symptoms (SAS) in adults with ≥5 years of T1D participating in the T1D Exchange from years 2010-2017. Associations of demographic, clinical, and laboratory factors with symptomatic DAN were assessed. RESULTS: Of the 4919 eligible T1D participants, 965 (20%) individuals completed the SAS questionnaire [mean age 40 ± 17 years, median diabetes duration 20 years (IQR: 13,34), 64% female, 90% non-Hispanic White, and 82% with private insurance]. DAN symptoms were present in 166 (17%) of responders with 72% experiencing moderate severity symptoms or worse. Symptomatic DAN participants had higher hemoglobin A1c (p = 0.03), longer duration (p = 0.004), were more likely to be female (p = 0.03), and more likely to have lower income (p = 0.03) versus no DAN symptoms. Symptomatic DAN was associated with diabetic peripheral neuropathy (p < 0.0001), smoking (p = 0.002), cardiovascular disease (p = 0.02), depression (p < 0.001), and opioid use (p = 0.004). CONCLUSIONS: DAN symptoms are common in T1D. Socioeconomic factors and psychological comorbidities may contribute to DAN symptoms and should be explored further.

Neuropsychological Outcomes in Individuals With Type 1 and Type 2 Diabetes.

Objective: To determine the prevalence of neuropsychological outcomes in individuals with type 1 diabetes compared to individuals with type 2 diabetes or without diabetes, and to evaluate the association of diabetes status and microvascular/macrovascular complications with neuropsychological outcomes. Patients and Methods: We used a nationally representative healthcare claims database of privately insured individuals (1/1/2001-12/31/2018) to identify individuals with type 1 diabetes. Propensity score matching was used as a quasi-randomization technique to match type 1 diabetes individuals to type 2 diabetes individuals and controls. Diabetes status, microvascular/macrovascular complications (retinopathy, neuropathy, nephropathy, stroke, myocardial infarction, peripheral vascular disease, amputations), and neuropsychological outcomes (mental health, cognitive, chronic pain, addiction, sleep disorders) were defined using ICD-9/10 codes. Logistic regression determined associations between diabetes status, microvascular/macrovascular complications, and neuropsychological outcomes. Results: We identified 184,765 type 1 diabetes individuals matched to 524,602 type 2 diabetes individuals and 522,768 controls. With the exception of cognitive disorders, type 2 diabetes individuals had the highest prevalence of neuropsychological outcomes, followed by type 1 diabetes, and controls. After adjusting for the presence of microvascular/macrovascular complications, type 1 diabetes was not significantly associated with a higher risk of neuropsychological outcomes; however, type 2 diabetes remained associated with mental health, cognitive, and sleep disorders. The presence of microvascular/macrovascular complications was independently associated with each neuropsychological outcome regardless of diabetes status. Conclusion: Microvascular/macrovascular complications are associated with a high risk of neuropsychological outcomes regardless of diabetes status. Therefore, preventing microvascular and macrovascular complications will likely help reduce the likelihood of neuropsychological outcomes either as the result of similar pathophysiologic processes or by preventing the direct and indirect consequences of these complications. For individuals with type 2 diabetes, risk factors beyond complications (such as obesity) likely contribute to neuropsychological outcomes.

Continuous Glucose Monitoring With Low-Carbohydrate Nutritional Coaching to Improve Type 2 Diabetes Control: Randomized Quality Improvement Program.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a leading cause of morbidity and mortality globally, with adverse health consequences largely related to hyperglycemia. Despite clinical practice guideline recommendations, effective pharmacotherapy, and interventions to support patients and providers, up to 60% of patients diagnosed with T2DM are estimated to have hemoglobin A1c (HbA1c) levels above the recommended targets owing to multilevel barriers hindering optimal glycemic control. OBJECTIVE: The aim of this study is to compare changes in HbA1c levels among patients with suboptimally controlled T2DM who were offered the opportunity to use an intermittently viewed continuous glucose monitor and receive personalized low-carbohydrate nutrition counseling (<100 g/day) versus those who received usual care (UC). METHODS: This was a 12-month, pragmatic, randomized quality improvement program. All adult patients with T2DM who received primary care at a university-affiliated primary care clinic (N=1584) were randomized to either the UC or the enhanced care (EC) group. Within each program arm, we identified individuals with HbA1c >7.5% (58 mmol/mol) who were medically eligible for tighter glycemic control, and we defined these subgroups as UC-high risk (UC-HR) or EC-HR. UC-HR participants (n=197) received routine primary care. EC-HR participants (n=185) were invited to use an intermittently viewed continuous glucose monitor and receive low-carbohydrate nutrition counseling. The primary outcome was mean change in HbA1c levels from baseline to 12 months using an intention-to-treat difference-in-differences analysis comparing EC-HR with UC-HR groups. We conducted follow-up semistructured interviews to understand EC-HR participant experiences with the intervention. RESULTS: HbA1c decreased by 0.41% (4.5 mmol/mol; P=.04) more from baseline to 12 months among participants in the EC-HR group than among those in UC-HR; however, only 61 (32.9%) of 185 EC-HR participants engaged in the program. Among the EC-HR participants who wore continuous glucose monitors (61/185, 32.9%), HbA1c was 1.1% lower at 12 months compared with baseline (P<.001). Interviews revealed themes related to EC-HR participants' program engagement and continuous glucose monitor use. CONCLUSIONS: Among patients with suboptimally controlled T2DM, a combined approach that includes continuous glucose monitoring and low-carbohydrate nutrition counseling can improve glycemic control compared with the standard of care.

Beliefs Around Hypoglycemia and Their Impacts on Hypoglycemia Outcomes in Individuals with Type 1 Diabetes and High Risks for Hypoglycemia Despite Using Advanced Diabetes Technologies.

OBJECTIVE: This study aimed to 1) identify the frequency of severe and level 2 hypoglycemia presenting in individuals with type 1 diabetes using continuous glucose monitoring systems (CGMs), including those with concomitant closed-loop insulin pumps, in a clinical practice setting and 2) evaluate the impact of beliefs around hypoglycemia in the development of severe and level 2 hypoglycemia in this population. RESEARCH DESIGN AND METHODS: A cross-sectional survey study in adults with type 1 diabetes using CGMs >6 months was conducted at a large tertiary academic center. Participant demographics, 6-month severe hypoglycemia history, hypoglycemia beliefs (with the Attitude to Awareness of Hypoglycemia questionnaire), and 4-week CGM glucose data were collected. Statistical analysis was performed to assess the presentation of severe and level 2 hypoglycemia and identify associated risk factors. RESULTS: A total of 289 participants were recruited (including 257 participants with CGM data within the last 3 months). Of these, 25.6% experienced at least one severe hypoglycemic episode in the last 6 months, and 13.6% presented with ≥1% of time in level 2 hypoglycemia on CGMs. Reporting beliefs about prioritizing hyperglycemia avoidance was associated with severe hypoglycemia development (P < 0.001), while having beliefs of minimal concerns for hypoglycemia was associated with spending ≥1% of time in level 2 hypoglycemia (P = 0.038). CONCLUSIONS: Despite the use of advanced diabetes technologies, severe and level 2 hypoglycemia continues to occur in individuals with type 1 diabetes and high hypoglycemia risks. Human factors, including beliefs around hypoglycemia, may continue to impact the effectiveness of glucose self-management.

Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19.

OBJECTIVE: Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear. RESEARCH DESIGN AND METHODS: We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. RESULTS: Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels. CONCLUSIONS: Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.

Dapagliflozin and measures of cardiovascular autonomic function in patients with type 2 diabetes (T2D).

AIMS: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce blood pressure without compensatory heart rate elevation, possibly by modulating sympathetic/parasympathetic activity. This may contribute to their cardiovascular benefits in type 2 diabetes (T2D). We evaluated the effects of dapagliflozin (DAPA) on measures of cardiovascular autonomic neuropathy (CAN), cardiac function, and glucose variability (GV) in T2D. METHODS: Pilot, randomized, two-period crossover trial comparing 12-week DAPA versus 12-week glimepiride treatment on CAN measures (cardiovascular autonomic reflex tests and heart rate variability), B-type natriuretic peptide (BNP), and GV (Abbott's Libre Pro devices) using signed rank tests and mixed models from baseline to 12 weeks within and between each period. RESULTS: Forty-five T2D participants on metformin monotherapy (mean age 57 ±â€¯8 years, duration 7 ±â€¯6 years, HbA1c 7.8 ±â€¯1.3%) were enrolled with 41 completing the trial. There were no differences in CAN indices or BNP with each drug compared to baseline and each other. Participants on DAPA demonstrated greater weight loss, reduced time in hypoglycemia, and improved GV compared to glimepiride. CONCLUSIONS: Short term treatment with DAPA did not affect CAN measures or BNP in uncomplicated and relatively healthy T2D participants. Longer prospective studies in patients with advanced disease are needed to better understand relationships between SGLT-2 inhibitors and CAN. CLINICAL TRIAL REGISTRATION: NCT02973477.

The Prevalence of Diabetic Microvascular Complications in China and the USA.

PURPOSE OF REVIEW: Diabetes can lead to development of devastating microvascular complications, such as nephropathy, retinopathy, and peripheral sensory and autonomic neuropathy. While China and the USA both face the threat of this major public health challenge, the literature is limited in describing similarities and differences in the prevalence, and risk factors for the development, of diabetic microvascular complications between these two countries. RECENT FINDINGS: The current review discusses the following: (1) the most recent evidence on prevalence of diabetic microvascular complications in China and the USA (including downtrends of diabetes retinopathy and neuropathy in the USA); (2) differences in patient risk factors of these complications; (3) challenges and current knowledge gaps (such as lacking national epidemiological data of diabetic complications in China); and (4) potential future clinical and research opportunities (including needs in diabetes evaluation and management in remote areas and standardization of methods in evaluating diabetic complications across countries). Diabetic microvascular complications remain to be health threats in both China and the USA. Further investigations are needed for comprehensive understanding and effect prevention and management of these complications.

Diabetes Distress and Glycemic Control in Type 2 Diabetes: Mediator and Moderator Analysis of a Peer Support Intervention.

BACKGROUND: High levels of psychosocial distress are correlated with worse glycemic control as measured by glycosylated hemoglobin levels (HbA1c). Some interventions specifically targeting diabetes distress have been shown to lead to lower HbA1c values, but the underlying mechanisms mediating this improvement are unknown. In addition, while type 2 diabetes mellitus (T2D) disproportionately affects low-income racial and ethnic minority populations, it is unclear whether interventions targeting distress are differentially effective depending on participants' baseline characteristics. OBJECTIVE: Our objective was to evaluate the mediators and moderators that would inform interventions for improvements in both glycemic control and diabetes distress. METHODS: Our target population included 290 Veterans Affairs patients with T2D enrolled in a comparative effectiveness trial of peer support alone versus technology-enhanced peer support with primary and secondary outcomes including HbA1c and diabetes distress at 6 months. Participants in both arms had significant improvements in both HbA1c and diabetes distress at 6 months, so the arms were pooled for all analyses. Goal setting, perceived competence, intrinsic motivation, and decisional conflict were evaluated as possible mediators of improvements in both diabetes distress and HbA1c. Baseline patient characteristics evaluated as potential moderators included age, race, highest level of education attained, employment status, income, health literacy, duration of diabetes, insulin use, baseline HbA1c, diabetes-specific social support, and depression. RESULTS: Among the primarily African American male veterans with T2D, the median age was 63 (SD 10.2) years with a baseline mean HbA1c of 9.1% (SD 1.7%). Improvements in diabetes distress were correlated with improvements in HbA1c in both bivariate and multivariable models adjusted for age, race, health literacy, duration of diabetes, and baseline HbA1c. Improved goal setting and perceived competence were found to mediate both the improvements in diabetes distress and in HbA1c, together accounting for 20% of the effect of diabetes distress on change in HbA1c. Race and insulin use were found to be significant moderators of improvements in diabetes distress and improved HbA1c. CONCLUSIONS: Prior studies have demonstrated that some but not all interventions that improve diabetes distress can lead to improved glycemic control. This study found that both improved goal setting and perceived competence over the course of the peer support intervention mediated both improved diabetes distress and improved HbA1c. This suggests that future interventions targeting diabetes distress should also incorporate elements to increase goal setting and perceived competence. The intervention effect of improvements in diabetes distress on glycemic control in peer support may be more pronounced among White and insulin-dependent veterans. Additional research is needed to understand how to better target diabetes distress and glycemic control in other vulnerable populations.

Continuous Glucose Monitoring With Low-Carbohydrate Diet Coaching in Adults With Prediabetes: Mixed Methods Pilot Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is preventable; however, few patients with prediabetes participate in prevention programs. The use of user-friendly continuous glucose monitors (CGMs) with low-carbohydrate diet coaching is a novel strategy to prevent T2DM. OBJECTIVE: This study aims to determine the patient satisfaction and feasibility of an intervention combining CGM use and low-carbohydrate diet coaching in patients with prediabetes to drive dietary behavior change. METHODS: We conducted a mixed methods, single-arm pilot and feasibility study at a suburban family medicine clinic. A total of 15 adults with prediabetes with hemoglobin A1c (HbA1c) levels between 5.7% and 6.4% and a BMI >30 kg/m2 were recruited to participate. The intervention and assessments took place during 3 in-person study visits and 2 qualitative phone interviews (3 weeks and 6 months after the intervention). During visit 1, participants were asked to wear a CGM and complete a food intake and craving log for 10 days. During visit 2, the food intake and craving log along with the CGM results of the participants were reviewed and the participants received low-carbohydrate diet coaching, including learning about carbohydrates and personalized feedback. A second CGM sensor, with the ability to scan and record glucose trends, was placed, and the participants logged their food intake and cravings as they attempted to reduce their total carbohydrate intake (<100 g/day). During visit 3, the participants reviewed their CGM and log data. The primary outcome was satisfaction with the use of CGM and low-carbohydrate diet. The secondary outcomes included feasibility, weight, and HbA1c change, and percentage of time spent in hyperglycemia. Changes in attitudes and risk perception of developing diabetes were also assessed. RESULTS: The overall satisfaction rate of our intervention was 93%. The intervention induced a weight reduction of 1.4 lb (P=.02) and a reduction of HbA1c levels by 0.71% (P<.001) since enrollment. Although not significantly, the percentage of time above glucose goal and average daily glucose levels decreased slightly during the study period. Qualitative interview themes indicated no major barriers to CGM use; the acceptance of a low-carbohydrate diet; and that CGMs helped to visualize the impact of carbohydrates on the body, driving dietary changes. CONCLUSIONS: The use of CGMs and low-carbohydrate diet coaching to drive dietary changes in patients with prediabetes is feasible and acceptable to patients. This novel method merits further exploration, as the preliminary data indicate that combining CGM use with low-carbohydrate diet coaching drives dietary changes, which may ultimately prevent T2DM.