The effect of continuous positive airway pressure on glucose excursions in diabetics with sleep-disordered breathing: the results of continuous glucose monitoring

Sleep-disordered breathing (SDB) is often associated with impaired glucose metabolism. The study aimed at assessing immediate effect of CPAP on glucose excursions in type 2 diabetic patients with SDB measured with 72-hour continuous glucose monitoring system (CGMS). 8 type 2 diabetic patients with SDB (men, age 48,13±4,91 years, BMI 34,06±7,41 kg·m–2, HbA1c 7,3±1,4%) underwent 2 overnight polysomnographic examinations including diagnostic night and CPAP night. CGMS was applied on both occasions. Statistical analyses included paired Student's t-test. CPAP decreased apnoea-hypopnoea index (AHI) from 57,64±9,64·h–1 to 8,05±4,42·h–1 (p<0,0001) with significant improvement of saturation. Frequent episodes of sleep apnoea/hypopnoea and severe oxygen desaturation were followed by significant rise in blood glucose of up to 12,3 mmol·l–1. Duration of post-hypoxic hyperglycemia was 50±10,79 min and its climax tended to be appeared up to 45min post-hypoxia. Nocturnal hyperglycemia strongly correlated with severe oxygen desaturation. Nocturnal glucose values were significantly higher during diagnostic night than during CPAP night (8,19±0,99 mmol·l–1 versus 6,77±1,47 mmol·l–1; p<0,0001). CGMS also showed improved preprandial and 1,5-hour postprandial glucose levels for breakfast after CPAP night. The improvement in overall glucose levels was much greater in patients with BMI<30 kg·m–2 than in more obese patients. The results suggest that nocturnal hyperglycemia is closely related to desaturation and CPAP treatment may have an immediate decreasing effect on blood glucose in type 2 diabetic patients with SDB

Power spectral analysis of respiratory responses to pharyngeal stimulation in cats: Comparisons with eupnoea and gasping

Based on similarities between properties of gasping and the aspiration reflex, we hypothesized that this reflex activates the central pattern generator for gasping. To evaluate this hypothesis, we have analysed high-frequency oscillations in phrenic and hypoglossal neural activities. These oscillations, analysed by power and coherence spectra, are considered as signatures of the central pattern generators for automatic ventilatory activity. In decerebrate, vagotomized, paralysed and ventilated cats, the aspiration reflex was elicited in eupnoea and gasping by mechanical stimulation of the pharynx and electrical stimulation of the glossopharyngeal nerve. Compared with eupnoeic values, the peaks in the power spectra occurred at higher frequencies in spontaneous gasping. Peaks in the coherence spectra showed identical changes. Power and coherence spectra of inspiratory neural activities during the aspiration reflex differed markedly from those of eupnoea, but were similar to those in gasping. We conclude that mechanical stimulation of the pharynx or electrical stimulation of the glossopharyngeal nerve activates a reflex by which the central pattern generator for eupnoea is depressed, and that for gasping is activated. Our results also support the concept that separate brainstem mechanisms generate ventilatory activity in eupnoea and gasping.link_to_subscribed_fulltex

An international, multicenter, observational survey to evaluate diabetes control in subjects using insulin for the treatment of type 1 and type 2 diabetes mellitus in the Czech Republic and Slovak Republic: study protocol for a cross-sectional survey

Jan Brož,1 Denisa Janickova Zdarska,1 Jana Urbanova,2 Marek Brabec,3 Bohumila Krivska,4 Viera Donicova,5 Radka Stepanova,6 Emil Martinka,7 Milan Kvapil1 1Department of Internal Medicine, Second Faculty of Medicine, 2Center for Research on Diabetes, Metabolism and Nutrition, Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, 3Institute of Computer Science of the ASCR, vvi, 4Sanofi, Prague, Czech Republic; 5Private Department of Diabetology, Internal Medicine and Metabolism, Kosice, Slovak Republic; 6ADDS sro, Brno, Czech Republic; 7National Institute of Endocrinology and Diabetology, Lubochna, Slovak Republic Background: Despite the improvements in insulin therapy, a large number of patients fail to achieve their target glycated hemoglobin (HbA1c) levels. Control of diabetes is often unsatisfactory because the patient does not know about the principles of successful insulin therapy (ie, blood glucose self-monitoring, the principles of insulin administration, titration, current dose adjustments, dietary recommendations, and physical activity preventive measures) or because these principles are applied incorrectly or insufficiently. Furthermore, the fear of hypoglycemia may lead to maintaining higher than recommended blood glucose levels. Methods/design: This is a noninterventional, international study focusing on a questionnaire survey of diabetes patients (patient-reported outcome) treated with insulin for at least 1 year. It is designed so that the data obtained reflect real access of patients to insulin treatment. The primary objective is to show the results of glycemic control of diabetes (HbA1c) achieved in diabetes patients treated with at least one dose of insulin. The secondary objective is to monitor the factors potentially affecting these results, which include the frequency and other characteristics of hypoglycemia, the frequency of blood glucose self-monitoring, and the effects produced when the results are employed in adjusting the therapy. Furthermore, the study investigates factors related to the principles of insulin administration, dietary regime, and exercise habits. The study will enroll a total of 1,500 patients with type 1 and type 2 diabetes in 150 centers: two-thirds in the Czech Republic and one-third in the Slovak Republic. Discussion: The study is primarily aimed at determining the percentage of insulin-treated diabetes patients reaching the recommended targets for glycemic control (HbA1c). Furthermore, it attempts to identify and describe in detail the factors of failure in achieving the therapeutic goals. An analysis of the data thus obtained may result in recommendations on how to reduce and eliminate all the identified negative factors in the future. Keywords: insulin therapy, glycemic control, HbA1c, hypoglycemia, education, diabetes regimen adherenc

Improved or comparable efficacy without increased hypoglycaemia with self- vs physician-led titration of insulin glargine 300 U/ml in age groups < 65 or >= 65 years: TAKE CONTROL

Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) (54th, 2018, Berlin, Germany

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial

Background: We aimed to assess efficacy and safety, with a special focus on cardiovascular safety, of the novel dual GIP and GLP-1 receptor agonist tirzepatide versus insulin glargine in adults with type 2 diabetes and high cardiovascular risk inadequately controlled on oral glucose-lowering medications. Methods: This open-label, parallel-group, phase 3 study was done in 187 sites in 14 countries on five continents. Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA1c) of 7·5–10·5% (58–91 mmol/mol), body-mass index of 25 kg/m2 or greater, and established cardiovascular disease or a high risk of cardiovascular events. Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL. The primary endpoint was non-inferiority (0·3% non-inferiority boundary) of tirzepatide 10 mg or 15 mg, or both, versus glargine in HbA1c change from baseline to 52 weeks. All participants were treated for at least 52 weeks, with treatment continued for a maximum of 104 weeks or until study completion to collect and adjudicate major adverse cardiovascular events (MACE). Safety measures were assessed over the full study period. This study was registered with ClinicalTrials.gov, NCT03730662. Findings: Patients were recruited between Nov 20, 2018, and Dec 30, 2019. 3045 participants were screened, with 2002 participants randomly assigned to tirzepatide or glargine. 1995 received at least one dose of tirzepatide 5 mg (n=329, 17%), 10 mg (n=328, 16%), or 15 mg (n=338, 17%), or glargine (n=1000, 50%), and were included in the modified intention-to-treat population. At 52 weeks, mean HbA1c changes with tirzepatide were −2·43% (SD 0·05) with 10 mg and −2·58% (0·05) with 15 mg, versus −1·44% (0·03) with glargine. The estimated treatment difference versus glargine was −0·99% (multiplicity adjusted 97·5% CI −1·13 to −0·86) for tirzepatide 10 mg and −1·14% (−1·28 to −1·00) for 15 mg, and the non-inferiority margin of 0·3% was met for both doses. Nausea (12–23%), diarrhoea (13–22%), decreased appetite (9–11%), and vomiting (5–9%) were more frequent with tirzepatide than glargine (nausea 2%, diarrhoea 4%, decreased appetite &lt;1%, and vomiting 2%, respectively); most cases were mild to moderate and occurred during the dose-escalation phase. The percentage of participants with hypoglycaemia (glucose &lt;54 mg/dL or severe) was lower with tirzepatide (6–9%) versus glargine (19%), particularly in participants not on sulfonylureas (tirzepatide 1–3% vs glargine 16%). Adjudicated MACE-4 events (cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina) occurred in 109 participants and were not increased on tirzepatide compared with glargine (hazard ratio 0·74, 95% CI 0·51–1·08). 60 deaths (n=25 [3%] tirzepatide; n=35 [4%] glargine) occurred during the study. Interpretation: In people with type 2 diabetes and elevated cardiovascular risk, tirzepatide, compared with glargine, demonstrated greater and clinically meaningful HbA1c reduction with a lower incidence of hypoglycaemia at week 52. Tirzepatide treatment was not associated with excess cardiovascular risk. Funding: Eli Lilly and Company