Incretins in patients with rheumatoid arthritis

Background: The precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients. Methods: We conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules between patients and control subjects. Results: Insulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity Score in 28 joints with erythrocyte sedimentation rate (? coefficient 46, 95% CI 6?87, p = 0.026) and Clinical Disease Activity Index (? coefficient 7.74, 95% CI 1.29?14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with ?-cell function (HOMA2 of ?-cell production calculated with C-peptide) in patients but not in control subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response. Conclusions: The incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA.This work was supported by grants from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 Instituto de Salud Carlos III [ISCIII] PI14/00394) and by the Fondo Europeo de Desarrollo Regional (FEDER) (to IFA). The research of MAGG was supported by European Union FEDER funds and by the “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748, PI12/00060, and PI15/00525) of the Instituto de Salud Carlos III (ISCIII; Spanish Health Ministry). The research of MAGG was also partially supported by RETICS Programs RD12/0009 (RIER) and RD12/0009/0013 from the ISCIII (Spanish Health Ministry)

The Biochemical and Cellular Basis for Nutraceutical Strategies to Attenuate Neurodegeneration in Parkinson’s Disease

Future therapeutic intervention that could effectively decelerate the rate of degeneration within the substantia nigra pars compacta (SNc) could add years of mobility and reduce morbidity associated with Parkinson’s disease (PD). Neurodegenerative decline associated with PD is distinguished by extensive damage to SNc dopaminergic (DAergic) neurons and decay of the striatal tract. While genetic mutations or environmental toxins can precipitate pathology, progressive degenerative succession involves a gradual decline in DA neurotransmission/synaptic uptake, impaired oxidative glucose consumption, a rise in striatal lactate and chronic inflammation. Nutraceuticals play a fundamental role in energy metabolism and signaling transduction pathways that control neurotransmission and inflammation. However, the use of nutritional supplements to slow the progression of PD has met with considerable challenge and has thus far proven unsuccessful. This review re-examines precipitating factors and insults involved in PD and how nutraceuticals can affect each of these biological targets. Discussed are disease dynamics (Sections 1 and 2) and natural substances, vitamins and minerals that could impact disease processes (Section 3). Topics include nutritional influences on α-synuclein aggregation, ubiquitin proteasome function, mTOR signaling/lysosomal-autophagy, energy failure, faulty catecholamine trafficking, DA oxidation, synthesis of toxic DA-quinones, o-semiquinones, benzothiazolines, hyperhomocyseinemia, methylation, inflammation and irreversible oxidation of neuromelanin. In summary, it is clear that future research will be required to consider the multi-faceted nature of this disease and re-examine how and why the use of nutritional multi-vitamin-mineral and plant-based combinations could be used to slow the progression of PD, if possible

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Can the devices used to treat obstructive sleep apnoea syndrome increase the tendency to gain weight?

Özet: Uyku apnesi tedavisinde kullan›lan cihazlar kilo almaya e¤ilimi artt›r›yor olabilir mi? Amaç: Bu çal›flma ile t›kay›c› uyku apnesi sendromu (TUAS) hastalar›-n›n tedavisinde kullan›lan cihazlar›n kilo de¤ifliklikleri üzerine etkilerinin araflt›r›lmas› planland›. Yöntem: Çal›flmaya horlama ve uyku apnesi flikayetleriyle baflvurup polisomnografi (PSG) tetkiki istenen 256 hasta dahil edildi. Hastalar apne hipopne indeksleri (AHI) ve cihaz kullan›m durumlar›na göre afla¤›daki flekilde grupland›r›ld›: Grup 1 TUAS tan›s› konularak tedavi amaçl› cihaz kullananlar (n=101), Grup 2 TUAS tan›s› konularak tedavi amaçl› önerilen cihaza uyum sa¤layamayanlar (n=76) ve Grup 3 PSG ile basit horlama teflhisi konulup TUAS olmayanlar (n=79). Grup 1; CPAP, Auto CPAP veya BiPap kullanan hastalardan oluflmaktad›r. Her üç grup hastan›n da vücut kitle indeksi (VK‹) ve boyun çevresi (BÇ) öl-çümleri kay›tlar›na PSG merkezinden ulafl›ld› (bafllang›ç de¤erleri); bu hastalar tekrar ölçüm ve kontrol için Kulak Burun Bo¤az poliklini¤ine ça¤›r›larak de¤erlendirildiler (kontrol de¤erleri). Bulgular: Grup 1 hastalar›nda; bafllang›ç de¤erleri ile kontrol de¤erleri karfl›laflt›r›ld›¤›nda: VK‹ ve BÇ istatistiksel olarak anlaml› derecede yük-sekti (p<0.05), Grup 2 ve 3 için VK‹ ve BÇ'de istatistiksel olarak anlaml› bir fark saptanmad› (p>0.05). Grup 1 de farkl› cihaz türlerini kullanan (CPAP, Auto CPAP veya BiPap) hastalar için VK‹ ve BÇ aç›s›ndan anlaml› farkl›l›k göstermedi (p>0.05). Sonuç: Uyku apnesi hastalar›n› tedavi etmek için kullan›lan cihazlar kilo almaya e¤ilimi artt›rmaktad›rlar. Bu hastalar›n ileride k›s›r dön-güye sebep olmamak için obezite aç›s›ndan yak›n takipleri ve gerekli önlemlerin al›nmas› gerekir. Anahtar sözcükler: Uyku apnesi, CPAP, Auto CPAP, BiPap, vücut kitle indeksi, boyun çevresi. Abstract Objective: This study investigated the effects of device treatments on weight changes in obstructive sleep apnoea syndrome (OSAS) patients. Methods: The study included 256 patients who underwent polysomnography to evaluate snoring and suspected OSAS. They were grouped according to the apnoea hypopnoea index (AHI) and device usage for OSAS as follows: Group 1 included patients who were established with OSAS diagnosis and used device for treatment purpose (n=101); Group 2 included patients who were established with OSAS diagnosis but could not adapt to the devices recommended for medical purposes (n=76); and Group 3 included patients who were established with ordinary snoring diagnosis but did not have OSAS, (n=79). Group 1 used CPAP, Auto CPAP, or BiPap. For all groups, BMI and neck circumference data were obtained from sleep centre records (baseline values) and invited to visit again for followup measurements in otolaryngology outpatient clinic (control values). Results: In Group 1, both BMI and neck circumference were increased at follow-up compared with the baseline measurements (p<0.05) while no significant change was detected in the other two groups (p>0.05). The BMI and neck circumference did not differ among the devices used in Group 1 (CPAP, Auto CPAP, and BiPap) (p>0.05). Conclusion: Devices used to treat OSAS tend to enhance weight gain. Such patients should be closely monitored and the required measures should be taken in terms of obesity