Long-Term Weight Change and Glycemic Control in Patients With Type 2 Diabetes Mellitus and Treated vs. Untreated Sleep-Disordered Breathing-Analysis From the DIAbetes COhoRtE.
ABSTRACT: Hypothesis: Positive airway pressure (PAP) is the standard treatment for sleep-disordered breathing (SDB), a prevalent condition in patients with type 2 diabetes mellitus (DM2). Recent studies showed that short-term PAP treatment may cause weight gain. However, long-term data for patients with DM2 are scarce. Therefore, the aim of the present analysis was to assess changes in weight and glycemic control in patients with DM2 and treated vs. untreated SDB. Methods: The DIAbetes COhoRtE (DIACORE) study is a prospective population-based cohort study in patients with DM2. At baseline, patients of the DIACORE-SDB sub-study were tested for SDB [defined as apnea-hypopnea-index (AHI) ≥ 15/h] using a two-channel ambulatory SDB-monitoring device. In this observational study, PAP treatment was initiated in a subgroup of patients with SDB (SDB PAP) within clinical routine between the baseline and first follow-up visit [median observation period of 2.3 (2.2; 2.4) years], whereas the other patients with SDB did not receive PAP (SDB untreated). At baseline and first follow-up visit, weight and HbA1c were assessed. Results: Of the 346 patients with SDB [mean age 68 years, 71% male, body-mass index (BMI) 31.9 kg/m2], 17% were in the SDB PAP and 83% in the SDB untreated group. Weight change within the observation period was similar in both groups (-0.2 and -0.9 kg; p = 0.322). The percentage of patients with severe weight gain (≥ 5 kg) within the observation period was significantly higher in the SDB PAP group compared to the SDB untreated group (15.0 vs. 5.6%; p = 0.011). Multivariable regression analysis, accounting for baseline HbA1c, insulin substitution, BMI, waist-to-hip ratio (WHR), physical activity, and AHI, showed that PAP treatment was significantly associated with a weight gain ≥ 5 kg [odds ratio (OR) = 3.497; 95% CI (1.343; 9.106); p = 0.010] and an increase in HbA1c [B = 2.410; 95% CI (0.118; 4.702); p = 0.039]. Conclusion: Median weight change was similar in patients with SDB with and without PAP treatment. However, patients with DM2 and PAP treatment have an increased risk of severe long-term weight gain and an increase in HbA1c. Clinical Trial registration: DRKS00010498.
Project description:<h4>Background</h4>Due to its prognostic importance for patients with type 2 diabetes (DM2), current guidelines recommend a systolic <130 mm Hg and diastolic <80 mm Hg blood pressure target. Periodic breathing, a form of sleep-disordered breathing, acutely causes repetitive hypoxia, sympathetic nervous system activation as well as oscillations of heart rate and blood pressure. However, limited data on the association of periodic breathing and control of blood pressure (BP) in patients with DM2 are available. Thus, the aim of the present study was to assess whether there is an association between periodic breathing and increased BP above the recommended target in DM2.<h4>Methods</h4>Cross-sectional data of 679 patients with DM2 from the DIACORE-SDB sub-study were analysed for association of periodic breathing with BP. Sleep-disordered breathing was assessed with a 2-channel ambulatory monitoring device including validated automatic pattern recognition for periodic breathing. BP values were determined in a standardized manner with three repeated measurements at rest.<h4>Results</h4>Of the 679 analysed individuals (61% male, age 66 ± 9 years, Body Mass Index [BMI] 31.0 ± 5.4 kg/m<sup>2</sup>), 11% had periodic breathing. Patients with periodic breathing had significantly higher systolic BP values (144 ± 19 mm Hg vs. 137 ± 18 mm Hg, p = 0.003). Multivariable regression analysis revealed that periodic breathing was associated with higher systolic BP (B [95% confidence interval, CI] = 4.4 [0.1; 8.7], p = 0.043) and not meeting the recommended BP target for patients with diabetes (<130/80 mmHg) (odds ratio, OR [95%CI] = 2.1 [1.1; 4.0], p = 0.026) independent of sex, age, high density lipoproteins, renal function, coronary heart disease and antihypertensive treatment.<h4>Conclusion</h4>Periodic breathing is associated with higher systolic BP in patients with DM2.
Project description:<h4>Introduction</h4>Patients with diabetes mellitus type 2 (DM2) are at high risk for micro- and macrovascular disease. Here, we explore the degree of traditional risk factor control in the baseline visit of a cohort of DM2 outpatients.<h4>Methods</h4>DIACORE (DIAbetes COhoRtE) is a prospective cohort study of 3000 adult DM2 outpatients. Here, we present results from the baseline visit. Sociodemographic and anthropometric variables, cardiovascular risk factors, comorbidities and medication were assessed by interview and medical exams. Serum-creatinine based estimated glomerular filtration rate (eGFRcrea) and urinary albumin-creatinine ratio (UACR) were determined for classification of chronic kidney disease (CKD). The proportion of patients with adequate control of traditional risk factors (blood pressure<140/90mmHg, HbA1c<7.5%, LDL<100mg/dl) was calculated in 2892 patients with non-missing data in 9 relevant variables within each KDIGO 2012 CKD class.<h4>Results</h4>In the analyzed baseline data (n = 2892, 60.2% men), mean (standard deviation) values for age, DM2 duration and HbA1c were 65.3 (9.3) years, 10.3 (8.4) years and 6.9% (1.1) respectively. Of these 2892 patients, 18.7% had CKD stage 3 or higher, 25.7% had UACR?30mg/g. Adequate blood pressure, HbA1c and LDL control was achieved in 55.7%, 78.5% and 34.4%, respectively. In 16.4% of patients (473), all three risk factors were below recommended targets. The proportion of adequate risk factor control was similar across KDIGO eGFRcrea classes. Adequate blood pressure and HbA1c control were significantly associated with lower UACR category without and with controlling for other risk factors (p<0.0001, p = 0.0002, respectively).<h4>Conclusion</h4>In our study of patients with diabetes mellitus type 2, we observed a low level of risk factor control indicating potential for risk reduction.
Project description:<h4>Background</h4>Diabetes mellitus type 2 (DM2) is highly associated with increased risk for chronic kidney disease (CKD), end stage renal disease (ESRD) and cardiovascular morbidity. Epidemiological and genetic studies generate hypotheses for innovative strategies in DM2 management by unravelling novel mechanisms of diabetes complications, which is essential for future intervention trials. We have thus initiated the DIAbetes COhoRtE study (DIACORE).<h4>Methods</h4>DIACORE is a prospective cohort study aiming to recruit 6000 patients of self-reported Caucasian ethnicity with prevalent DM2 for at least 10 years of follow-up. Study visits are performed in University-based recruiting clinics in Germany using standard operating procedures. All prevalent DM2 patients in outpatient clinics surrounding the recruiting centers are invited to participate. At baseline and at each 2-year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized online questionnaire and physical examination to determine incident micro- and macrovascular DM2 complications, malignancy and hospitalization, with a primary focus on renal events. Confirmatory outcome information is requested from patient records. Blood samples are obtained for a centrally analyzed standard laboratory panel and for biobanking of aliquots of serum, plasma, urine, mRNA and DNA for future scientific use. A subset of the cohort is subjected to extended phenotyping, e.g. sleep apnea screening, skin autofluorescence measurement, non-mydriatic retinal photography and non-invasive determination of arterial stiffness.<h4>Discussion</h4>DIACORE will enable the prospective evaluation of factors involved in DM2 complication pathogenesis using high-throughput technologies in biosamples and genetic epidemiological studies.
Project description:<h4>Background</h4>Right-heart dysfunction is associated with poor prognosis in heart failure with preserved left ventricular ejection fraction (HFpEF). It remains unclear whether sleep-disordered breathing (SDB) treatment using positive airway pressure (PAP) improves right-heart and pulmonary function and exercise capacity and reduces mortality rates of HFpEF patients.<h4>Hypothesis</h4>PAP may improve right-heart and pulmonary function, exercise capacity and prognosis in HFpEF patients with SDB.<h4>Methods</h4>One hundred nine consecutive patients with HFpEF (left ventricular ejection fraction >50%) and moderate to severe SDB (apnea-hypopnea index ≥15/h) treated with medications were divided into 2 groups: 31 patients with PAP (PAP group) and 78 patients without PAP (non-PAP group). Right ventricular fractional area change (RV-FAC), tricuspid valve regurgitation pressure gradient (TR-PG), tricuspid valve E/E', forced expiratory volume in 1 second/forced vital capacity (FEV1 /FVC), percentage of vital capacity, and peak VO2 were determined before and 6 months later, and all-cause mortality was followed up for 916 days.<h4>Results</h4>All parameters improved in the PAP group (RV-FAC, 36.0% -46.5%; TR-PG, 31.1 mm Hg-22.4 mm Hg; tricuspid valve E/E', 7.8-5.1; FEV1 /FVC, 83.9%-89.8%; percentage of vital capacity, 83.5%-89.9%; and peak VO2 , 16.6 mL/kg/min-19.6 mL/kg/min; P <0.05, respectively) but not in the non-PAP group. Importantly, all-cause mortality was significantly lower in the PAP group than in the non-PAP group (0% vs 12.8%; log-rank P = 0.014).<h4>Conclusions</h4>Positive airway pressure improves right-heart and pulmonary function and exercise capacity and may reduce all-cause mortality in patients with HFpEF and SDB.
Project description:The aims of the study were to determine whether mild, occult sleep-disordered breathing (SDB) moderates the efficacy of cognitive behavioral therapy for insomnia (CBTI) in older adults and to explore whether CBTI reduces the number of patients eligible for positive airway pressure (PAP) therapy.Data were analyzed for 134 adults 60 years or older with insomnia and apnea-hypopnea index (AHI) of less than 15 who were randomized to a larger study of CBTI versus a sleep education control. Sleep outcomes (sleep onset latency, total wake time, wake after sleep onset, sleep efficiency, Pittsburgh Sleep Quality Index) were compared between CBTI and control at 6 months using repeated-measures analysis of variance adjusted for baseline values. AHI of 5 or greater versus less than 5 was included as an interaction term to evaluate changes in sleep outcomes. The number of participants at baseline and 6 months with mild SDB for whom insomnia was their only other indication for PAP was also compared between CBTI and control.AHI status (AHI ? 5 [75.5% of participants] versus AHI < 5) did not moderate improvements in sleep associated with CBTI (all p values ? .12). Nine (45.0%) of 20 participants with mild SDB for whom insomnia was their only other indication for PAP therapy at baseline no longer had another indication for PAP at 6 months, with no significant difference between CBTI and control.CBTI improves sleep in older veterans with insomnia and untreated mild SDB. Larger trials are needed to assess whether CBTI reduces the number of patients with mild SDB eligible for PAP.
Project description:An active device that downregulates abdominal vagal signalling has resulted in significant weight loss in feasibility studies.To prospectively evaluate the effect of intermittent vagal blocking (VBLOC) on weight loss, glycemic control, and blood pressure (BP) in obese subjects with DM2.Twenty-eight subjects were implanted with a VBLOC device (Maestro Rechargeable System) at 5 centers in an open-label study. Effects on weight loss, HbA1c, fasting blood glucose, and BP were evaluated at 1 week to 12 months.26 subjects (17 females/9 males, 51 ± 2 years, BMI 37 ± 1?kg/m(2), mean?±?SEM) completed 12 months followup. One serious adverse event (pain at implant site) was easily resolved. At 1 week and 12 months, mean excess weight loss percentages (% EWL) were 9 ± 1% and 25 ± 4% (P < 0.0001), and HbA1c declined by 0.3 ± 0.1% and 1.0 ± 0.2% (P = 0.02, baseline 7.8 ± 0.2%). In DM2 subjects with elevated BP (n = 15), mean arterial pressure reduced by 7 ± 3?mmHg and 8 ± 3?mmHg (P = 0.04, baseline 100 ± 2?mmHg) at 1 week and 12 months. All subjects MAP decreased by 3 ± 2?mmHg (baseline 95 ± 2?mmHg) at 12 months.VBLOC was safe in obese DM2 subjects and associated with meaningful weight loss, early and sustained improvements in HbA1c, and reductions in BP in hypertensive DM2 subjects. This trial is registered with ClinicalTrials.gov NCT00555958.
Project description:<h4>Purpose</h4>To evaluate the impact of the COVID-19 pandemic on non-invasive positive airway pressure (PAP) usage among children with sleep-disordered breathing (SDB).<h4>Methods</h4>PAP usage data in children with SDB aged 1 to 18 years old at The Hospital for Sick Children, Canada, were analyzed. The PAP usage data were recorded for 3 months prior to and 3 months following the COVID-19 lockdown in Ontario, Canada. The primary outcomes of interest were (i) percentage of days that PAP was used for ≥ 4 h and (ii) average daily usage of PAP based on days when PAP was used.<h4>Results</h4>A total of 151 children were included. The mean (± SD) age and BMI were 12.6 ± 4.1 years and 28.7 ± 12.4 kg/m<sup>2</sup>, respectively. The median (IQR) percentage of days of PAP usage for ≥ 4 h and average nightly PAP usage was significantly higher during compared with prior to the pandemic (76.7 [19.0-94.0] vs 62.0 [15.5-89.0]%, p = 0.02, and 406.0 [244.0-525.0] vs 367.0 [218.0-496.0] min, p = 0.006, respectively). Within this cohort, 95/151 (63%) children with SDB showed increased PAP usage and 56/151 (37%) either decreased the amount of time they used PAP or stopped PAP use altogether.<h4>Conclusions</h4>COVID-19 pandemic has provided opportunities for increased PAP usage in a significant number of children with SDB. A subset of children with prior evidence for suboptimal PAP usage showed further decreases in PAP usage during the pandemic. This information is critical for clinicians to provide anticipatory guidance to encourage PAP usage both during the pandemic and beyond.
Project description:INTRODUCTION:Despite the high prevalence of sleep-disordered breathing (SDB) and the significant health consequences associated with untreated disease, access to diagnosis and treatment remains a challenge. Even patients with severe SDB (severe obstructive sleep apnoea or hypoventilation), who are at particularly high risk of adverse health effects, are subject to long delays. Previous research has demonstrated that, within a sleep clinic, management by alternative care providers (ACPs) is effective for patients with milder forms of SDB. The purpose of this study is to compare an ACP-led clinic (ACP Clinic) for patients with severe SDB to physician-led care, from the perspective of clinical outcomes, health system efficiency and cost. METHODS AND ANALYSIS:The study is a randomised, controlled, non-inferiority study in which patients who are referred with severe SDB are randomised to management by a sleep physician or by an ACP. ACPs will be supervised by sleep physicians for safety. The primary outcome is positive airway pressure (PAP) adherence after 3?months of therapy. Secondary outcomes include: long-term PAP adherence; clinical response to therapy; health-related quality of life; patient satisfaction; healthcare usage; wait times from referral to treatment initiation and cost-effectiveness. The economic analysis will be performed using the perspective of a publicly funded healthcare system. ETHICS AND DISSEMINATION:Ethics approval was obtained from the Conjoint Health Research Ethics Board (ID: REB13-1280) at the University of Calgary. Results from this study will be disseminated through presentations at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER:NCT02191085; Pre-results.
Project description:Diabetes Mellitus type 2 (DM2) is associated with increased cancer risk. Instability of the genetic material plays a key role in the aetiology of human cancer. This study aimed to analyse genomic instability with the micronucleus cytome assay in exfoliated buccal cells depending on glycated haemoglobin (HbA1c) levels and medication in 146 female DM2 patients. The occurrence of micronuclei was significantly increased in DM2 patients compared to healthy controls. Furthermore, it was doubled in DM2 patients with HbA1c?>?7.5% compared to subjects with HbA1c???7.5%. Positive correlations were found between micronuclei frequencies and HbA1c as well as fasting plasma glucose. Patients under insulin treatment showed a two-fold increase in micronuclei frequencies compared to subjects under first-line medication (no drugs or monotherapy with non-insulin medication). However, after separation of HbA1c (cut-off 7.5%) only patients with severe DM2 characterised by high HbA1c and insulin treatment showed higher micronuclei frequencies but not patients with insulin treatment and low HbA1c. We demonstrated that the severity of DM2 accompanied by elevated micronuclei frequencies predict a possible enhanced cancer risk among female DM2 patients. Therapy, therefore, should focus on a strict HbA1c control and personalised medical treatments.
Project description:Sleep disordered breathing (SDB) is common in heart failure patients across the range of ejection fractions and is associated with adverse prognosis. Although effective pharmacologic and device-based treatment of heart failure may reduce the frequency or severity of SDB, heart failure treatment alone may not be adequate to restore normal breathing during sleep. Continuous positive airway pressure (CPAP) is the major treatment for SDB in heart failure, especially if obstructive rather than central sleep apnea (CSA) predominates. Adequate suppression of CSA by PAP is associated with a heart transplant-free survival benefit, although randomized trials are ongoing. Bilevel PAP (BPAP) may be as effective as CPAP in treating SDB and may be preferable over CPAP in patients who experience expiratory pressure discomfort. Adaptive (or auto) servo-ventilation (ASV), which adjusts the PAP depending on the patient's airflow or tidal volume, may be useful in congestive heart failure patients if CPAP is ineffective. Other therapies that have been proposed for SDB in congestive heart failure include nocturnal oxygen, CO(2) administration (by adding dead space), theophylline, and acetazolamide; most of which have not been systematically studied in outcome-based prospective randomized trials.