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Patients (pts) (n=1012) with T2D (A1C 7-11%) on oral antidiabetic drugs (OADs) were randomized 1:1 to open label IDegLira or IGlar U100 in a 104 week trial to assess treatment durability. The primary endpoint was time from randomization to treatment intensification (A1C ≥7.0% at 2 consecutive visits including week 26); pts who met the primary endpoint discontinued study drug. Baseline characteristics were similar. Over 104 weeks, fewer pts with IDegLira required intensification vs. IGlar U100 (37.4% vs. 66.2%). Pts treated with IDegLira had a significantly longer time to intensification (median: >2 years/~1 year for IDegLira/IGlar U100; Figure). There was greater effect with IDegLira vs. IGlar U100 after 104 weeks, had intensification not been needed, in terms of: pts achieving A1C <7% (55.7 vs. 28.5%), and A1C <7% with no weight gain (20.9 vs. 6.3%), lower estimated mean insulin dose (36 vs. 51 U; estimated treatment difference -14.9 U), and 56% lower rate of severe or blood glucose confirmed symptomatic hypoglycemia (0.38 vs. 0.86 events/patient-year of exposure, (p<0.0001 for all). Safety results were similar. Improved long-term glycemic control, evidenced by significantly longer time to treatment intensification, was achieved with IDegLira vs. IGlar U100 in pts previously uncontrolled on OADs. Disclosure: V.R. Aroda: Consultant; Self; ADOCIA, AstraZeneca, Becton, Dickinson and Company, Novo Nordisk Inc., Sanofi, Zafgen, Inc. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; AstraZeneca, Calibra Medical, Eisai Inc., Janssen Research & Development, Novo Nordisk Inc., Sanofi, Theracos, Inc. G. Gonzalez-Galvez: Advisory Panel; Self; Amgen Inc., AstraZeneca, Janssen Pharmaceuticals, Inc., Metabolic Solutions Development Company, Novo Nordisk A/S, Sanofi-Aventis, Takeda Pharmaceutical Company Limited. Consultant; Self; Amgen Inc., AstraZeneca, Janssen Pharmaceuticals, Inc., Metabolic Solutions Development Company, Novo Nordisk A/S, Sanofi-Aventis, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Metabolic Solutions Development Company, Novo Nordisk A/S, Sanofi-Aventis, Takeda Pharmaceutical Company Limited. M. Haluzik: Advisory Panel; Self; AstraZeneca, Medtronic, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Johnson & Johnson, Lilly Diabetes. Speaker's Bureau; Self; Novartis AG. R.J. Silver: Consultant; Self; Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S. R. Grøn: Employee; Self; Novo Nordisk A/S. N. Halladin: Employee; Self; Novo Nordisk A/S. P. Örsy: Employee; Self; Novo Nordisk A/S. G. Sesti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, GlaxoSmithKline plc., Novo Nordisk A/S, Servier. Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, GlaxoSmithKline plc., Novo Nordisk A/S, Servier. Funding: Novo Nordisk A/S [ABSTRACT FROM AUTHOR]

Objective: We tested the effects of two energy- and macronutrient-matched meals: a standard meat (M-meal) and a vegan (V-meal) on postprandial incretin and insulin secretion in participants with type 2 diabetes (T2D). Research Design and Methods: A randomized crossover design was used in 20 participants with T2D. Plasma concentrations of glucose, insulin, C-peptide, glucagon-like peptide -1 (GLP-1), amylin, and gastric inhibitory peptide (GIP) were determined at 0, 30, 60, 120 and 180 minutes. Beta-cell function was assessed with a mathematical model, using C-peptide deconvolution. Repeated-measures ANOVA was used for statistical analysis. Results: Postprandial plasma glucose responses were similar after both test meals (p=0.64). An increase in the stimulated secretion of insulin (by 30.5%; 95% CI 21.2 to 40.7%; p<0.001), C-peptide (by 7.1%; 95% CI 4.1 to 9.9%; p<0.001), and amylin (by 15.7%; 95% CI 11.8 to 19.7%; p<0.001) was observed following consumption of the V-meal. An increase in stimulated secretion of GLP-1 (by 19.2%; 95% CI 12.4 to 26.7%; p<0.001) and a decrease in GIP (by -9.4%; 95% CI -17.3 to -0.7%; p=0.02) were observed after the V-meal. Several parameters of beta-cell function increased after the V-meal, particularly insulin secretion at a fixed glucose value 5 mmol/L, rate sensitivity, and the potentiation factor. Conclusions: Our results indicate an increase in postprandial incretin and insulin secretion, following consumption of a single vegan meal, suggesting a therapeutic potential of plant-based meals for improving beta-cell function in T2D. Disclosure: H. Kahleova: None. A. Tura: None. M. Klementova: None. L. Belinova: None. M. Haluzik: None. R. Pavlovicova: None. M. Hill: None. T. Pelikanova: None. Funding: Ministry of Health of the Czech Republic (AZV15-27338A); Institute for Clinical and Experimental Medicine (MZCR00023001) [ABSTRACT FROM AUTHOR]

The duodenum has recently emerged as a key regulator in glucose metabolism via modulation of a complex network of neural and hormonal signals in response to ingested food. DiaGone™ is an endoscopic device which utilizes precisely controlled laser technology to target the duodenal submucosal neural plexi with the aim of improving glucose control by modulating the gastrointestinal neurohumoral axis. Nine subjects (5 males) with obesity (BMI 34.0 ± 4.6 kg/m2) and type 2 diabetes mellitus (T2DM) insufficiently controlled on metformin were included in this first-in-human trial in order to assess the efficacy and safety of DiaGone™. Subjects were instructed to continue with regular diet 24h after the procedure and metformin dose was not changed during the study period. Biochemical and anthropometric parameters were assessed at baseline and 3 and 6 months after the procedure and continuous glucose monitoring (CGM) and a standard liquid meal test were performed at baseline and 3 months after the procedure. DiaGone™ significantly decreased HbA1C from 78.3 ± 13.3 mmol/mol at baseline to 64.9 ± 6.4 mmol/mol and 64.8 ± 7.1 mmol/mol at 3 and 6 months, respectively (p<0.01). Similarly, a decrease in fasting glucose levels was noted (12.4 ± 3.5 vs. 9.5 ± 2.0 vs. 9.7 ± 2.7 mmol/l, p<0.01) with no significant changes in fasting insulin levels. Glucose AUC during the 150 min meal test 3 months after the procedure showed a reduction of 20% from baseline (43,435 vs. 34,096, p<0.01). No significant changes were observed in AUC for insulin. No adverse events related to the procedure or significant changes in weight were reported throughout the 6-month period. In conclusion, these pilot results suggest that endoscopic duodenal submucosal laser ablation using the DiaGone™ device is associated with improvements in both baseline and postprandial glycemia as well as HbA1C with no significant changes in insulin levels or body weight while having a favorable safety and tolerability profile. Disclosure: M. Mraz: None. I. Marcovitch: Employee; Self; Digma Medical. I. Lankova: None. H. Kratochvilova: None. A. Cinkajzlova: None. M. Benes: None. J. Korner: Board Member; Self; Digma Medical. Stock/Shareholder; Self; Digma Medical. Z. Vlasakova: None. J. Spicak: None. T. Pelikanova: None. M. Haluzik: None. Funding: MH CZ - DRO; Institute for Clinical and Experimental Medicine (IN00023001); RVO (VFN64165) [ABSTRACT FROM AUTHOR]

Studies directly comparing metabolic efficacy of various sodium glucose cotransporter-2 inhibitors (SGLT2i) are scarce. To this end, we compared the effect of SGLT2i: Empagliflozin (EMP), Canagliflozin (CAN) and Dapagliflozin (DAP) on biometric, metabolic and hormonal parameters and insulin sensitivity in hereditary hypertriglyceridemic rats (hHTG) - a non-obese model of metabolic syndrome characterized by dyslipidemia, insulin resistance and increased blood pressure. Male rats, 4 months old, were fed standard diet (C) or standard diet enriched by EMP (10mg/kg b.w./day), CAN (100mg/kg b.w./day) or DAP (10mg/kg b.w./day) for 6 weeks. All SGLT2i induced glycosuria which was 8-fold higher in CAN and DAP as compared to EMP group (Mean±SD: EMP:53±6; CAN:416±4; DAP:376±32 mmol/l; P<0.001). CAN decreased body weight relative to C while EMP and DAP had no significant effect. Visceral fat weight decreased in CAN and DAP compared to C (P<0.01). Relative weight of kidneys (g/100g b.w.) was increased in all SGLT2i groups compared to C with a less pronounced effect of EMP relative to CAN and DAP (P<0.01). CAN decreased both fasting and postprandial glycemia relative to other groups. Postprandial triglyceride levels were decreased by all SGLT2i compared to C (EMP: -32%; P<0.01; CAN: -55%; DAP -48%, P<0.001). 14C-palmitic acid oxidation decreased in the myocardium of CAN and DAP compared to C, whereas no significant effect of EMP was noted. CAN and EMP administration reduced liver glycogen content compared to C (P<0.05). Leptin levels decreased in CAN (-79%) and DAP (-56%) compared to C. GLP-1 levels increased in CAN compared to other groups while C-peptide was lower in CAN vs. C group. In conclusion, our results suggest higher efficacy of CAN compared to DAP and EMP in improving insulin sensitivity and decreasing glucose levels in a non-obese model of metabolic syndrome. The differences could be related to higher SGLT1 inhibition activity of CAN. Disclosure: J. Trnovska: None. M. Hüttl: None. I. Marková: None. O. Oliyarnyk: None. H. Malinska: None. D. Miklankova: None. H. Kratochvilova: None. P. Svoboda: None. A. Cinkajzlova: None. I. Lankova: None. M. Mraz: None. M. Haluzik: None. Funding: MH CZ - DRO; Institute for Clinical and Experimental Medicine (IN00023001) [ABSTRACT FROM AUTHOR]

Objective: Gastrointestinal hormones play a key role in glucose metabolism and satiety. We examined the acute effect of meal composition on these hormones in three population groups. Research Design and Methods: A randomized crossover design was used to test the effects of two energy- and macronutrient-matched meals: a processed-meat (M-meal) and a vegan (V-meal) on gastrointestinal hormones, and satiety in participants with type 2 diabetes (T2D, n=20), obese participants (O, n=20), and healthy controls (H, n=20). Plasma concentrations of glucagon-like peptide -1 (GLP-1), amylin, and peptide YY (PYY) were determined at 0, 30, 60, 120 and 180 minutes. Satiety was assessed using a visual analogue scale. Repeated-measures ANOVA was used for statistical analysis. Results: An increase in postprandial secretion of GLP-1 was observed after the V-meal in T2D (by 30.5%; 95% CI 21.2 to 40.7%; p<0.001) and H (by 15.8%; 95% CI 8.6 to 23.5%; p=0.01). An increase in postprandial plasma concentrations of amylin was observed in all groups after the V-meal: by 15.7% in T2D (95% CI 11.8 to 19.6%; p<0.001); by 11.5% in O (95% CI 7.8 to 15.3%; p=0.03); and by 13.8% in H (95% CI 8.4 to 19.5%; p<0.001). An increase in postprandial values of PYY after the V-meal was significant only in H (by 18.9%; 95% CI 7.5 to 31.3%; p=0.03). The participants in all groups reported greater satiety after the V-meal: by 9.0% in T2D (95% CI 4.4 to 13.6%; p=0.004); by 18.7% in O (95% CI 12.8 to 24.6%; p<0.001); and by 25.0% in H (95% CI 18.2 to 31.7%; p<0.001). Conclusions: Our results indicate there is an increase in gut hormones and satiety, following consumption of a single plant-based meal when compared with an energy- and macronutrient-matched standard meat meal. Disclosure: J. Veleba: None. M. Klementova: None. L. Belinova: None. M. Haluzik: None. R. Pavlovicova: None. M. Hill: None. T. Pelikanova: None. H. Kahleova: None. Funding: Ministry of Health of the Czech Republic (AZV15-27338A); Institute for Clinical and Experimental Medicine (MZCR00023001) [ABSTRACT FROM AUTHOR]

Diminished postprandial secretion of incretins and insulin represents one of the key pathophysiological mechanisms behind type 2 diabetes (T2D). We tested the effects of two energy- and macronutrient-matched meals: A standard meat (M-meal) and a vegan (V-meal) on postprandial incretin and insulin secretion in participants with T2D. A randomized crossover design was used in 20 participants with T2D. Plasma concentrations of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), amylin, and gastric inhibitory peptide (GIP) were determined at 0, 30, 60, 120, and 180 min. Beta-cell function was assessed with a mathematical model, using C-peptide deconvolution. Repeated-measures ANOVA was used for statistical analysis. Postprandial plasma glucose responses were similar after both test meals (p = 0.64). An increase in the stimulated secretion of insulin (by 30.5%; 95% CI 21.2 to 40.7%; p < 0.001), C-peptide (by 7.1%; 95% CI 4.1 to 9.9%; p < 0.001), and amylin (by 15.7%; 95% CI 11.8 to 19.7%; p < 0.001) was observed following consumption of the V-meal. An increase in stimulated secretion of GLP-1 (by 19.2%; 95% CI 12.4 to 26.7%; p < 0.001) and a decrease in GIP (by −9.4%; 95% CI −17.3 to −0.7%; p = 0.02) were observed after the V-meal. Several parameters of beta-cell function increased after the V-meal, particularly insulin secretion at a fixed glucose value 5 mmol/L, rate sensitivity, and the potentiation factor. Our results showed an increase in postprandial incretin and insulin secretion, after consumption of a V-meal, suggesting a therapeutic potential of plant-based meals for improving beta-cell function in T2D. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and decrease the risk of cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute to the development of heart failure. We aimed to elucidate a possible role of changes in EAT metabolic and inflammatory profile in the beneficial cardioprotective effects of SGLT-2i in subjects with severe heart failure. Methods: 26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 ± 2.1 vs. 55.3 ± 2.1 years, n.s.), body mass index (27.8 ± 0.9 vs. 28.8 ± 1.0 kg/m2, n.s.) and left ventricular ejection fraction (20.7 ± 0.5 vs. 23.2 ± 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed. Results: SGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects. Conclusions: Our results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure. [ABSTRACT FROM AUTHOR]

Despite the availability of various antihyperglycaemic therapies and comprehensive guidelines, glycaemic control in diabetes management has not improved significantly during the last decade in the real-world clinical setting. Treatment inertia arising from a complex interplay among patient-, clinician- and healthcare-system-related factors is the prime reason for this suboptimal glycaemic control. Also, the key factor leading to inadequate glycaemic levels remains limited communication between healthcare professionals (HCPs) and people with type 2 diabetes (PwT2D). Early insulin administration has several advantages including reduced glucotoxicity, high efficacy and preserved β-cell mass/function, leading to lowering the risk of diabetes complications. The current publication is based on consensus of experts from the South-Eastern European region and Israel who reviewed the existing evidence and guidelines for the treatment of PwT2D. Herein, the experts emphasised the timely use of insulin, preferably second-generation basal insulin (BI) analogues and intensification using basal-plus therapy, as the most-potent glucose-lowering treatment choice in the real-world clinical setting. Despite an increase in the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), the experts urged timely insulin initiation for inadequate glycaemic control in PwT2D. Furthermore, the combination of BI and GLP-1 RA addressing both fasting plasma glucose and post-prandial excursions as a free- or fixed-ratio combination was identified to reduce treatment complexity and burden. To minimise discontinuation and improve adherence, the experts reiterated quality, regular interactions and discussions between HCPs and PwT2D/carers for their involvement in the diabetes management decision-making process. Clinicians and HCPs should consider the opinions of the experts in accordance with the most recent recommendations for diabetes management. [ABSTRACT FROM AUTHOR]

Increased blood glucose levels frequently occur in critically ill patients. Numerous studies have shown that its normalization by intensive insulin treatment markedly improve their outcome. The aim of our study was to compare blood glucose control by the fully automated model predictive control algorithm with variable sampling rate (eMPC) with routine glucose management protocol (RMP) in peri- and postoperative period in cardiac surgery patients. 60 patients (43 men and 17 women; mean age 68±10 years; mean BMI 27.2±4.6 kg/m²) were included into the study, 30 were randomized for treatment using eMPC algorithm and 30 using RMP. All patients underwent elective cardiac surgery and were treated with continuous insulin infusion to maintain euglycemia (target range 4.4 - 6.1 mmol/l). Blood glucose was measured in 1-4 hour intervals depending on request of each algorithm during surgery and post-operation period for 24 hours. Mean blood glucose was 6.15 ± 1.11 mmol/l in eMPC group vs. 7.21 ±1.08 mmol/l in RMP group (p<0.05); percentage of time in target range was 60.4 ± 22.8% for eMPC vs. 27.5 ±16.2% for RMP group (p<0.05). Percentage of time above target range was 30.8 ± 19.6% vs. 69.6 ± 17.1% (p<0,05). No severe hypoglycemia (blood glucose bellow 2.9 mmol/l) was observed during the study. Average insulin infusion rate was 4.67 ± 3.34 in eMPC vs. 2.57 ± 1.66 IU/h in RMP (p<0.05), average sampling interval was 1.46 ± 0.31 vs. 2.10 ± 0.22 hours (p<0.05). We conclude that eMPC algorithm was more effective and comparably safe as compared to RMP in maintaining euglycemia in cardiac surgery patients. [ABSTRACT FROM AUTHOR]

Backgrounds: Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) may be involved in pathogenesis of gestational diabetes mellitus (GDM). The aim was to compare GLP-1 and GIP production in fasting state and during 3 h mixed meal tolerance test (MMTT) measured by mean area under the curve (AUC) between pregnant women with normal and impaired fasting glucose in an early phase of pregnancy, and healthy non-pregnant controls. Methods: This study was undertaken as a case–control study. Repeated measurement of fasting plasma glucose ≥ 5.1 mmol/L and < 7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes according to IADSPG criteria was used to find women with impaired fasting glucose (n = 22). Age-matched controls consisted of healthy pregnant (n = 25) and non-pregnant (n = 24) women. In addition to incretins, anthropometric parameters and markers of insulin resistance and beta-cell function were assessed. Variables were summarized as median (interquartile range). Results: Fasting GLP-1 and GIP concentration or their AUC during MMTT did not significantly differ between pregnant women with impaired fasting plasma glucose [GLP-1AUC 19.0 (53.1) and GIPAUC 302 (100) pg/mL/min] and healthy pregnant women [GLP-1AUC 16.7 (22.3) and GIPAUC 297 (142) pg/mL/min] or non-pregnant controls [GLP-1AUC 16.8 (9.8) and for GIPAUC 313 (98) pg/mL/min]. Although women with impaired fasting glucose were more obese and showed decreased beta-cell function, there were not significant correlations between incretin production and parameters of insulin secretion, insulin resistance, or obesity. Conclusions: Women with impaired fasting plasma glucose did not show altered incretin production in the first trimester of pregnancy. In contrast to type 2 diabetes, impaired incretin secretion does not seem to play a major role in the early development of GDM. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1) receptor agonists mimic the action of the endogenous GLP-1 incretin hormone, improving glycaemic control in type 2 diabetes mellitus (T2DM) by increasing insulin secretion and decreasing glucagon secretion in a glucose-dependent manner. However, as cardiovascular (CV) morbidity and mortality is common in patients with T2DM, several trials with the use of GLP-1 receptor agonists (RAs) have been performed focusing on endpoints related to cardiovascular disease rather than metabolic control of T2DM. Following the positive cardiovascular effects of liraglutide, dulaglutide and semaglutide observed in these trials, major changes in T2DM management guidelines have occurred. This document from a Eastern and Southern European Diabetes Expert Group discusses the results of GLP-1 RA CV outcomes trials, their impact on recent clinical guidelines for the management of T2DM, and some selected combination regimens utilising GLP-1 RAs. We also propose an algorithm for guiding GLP-1 RA-based treatment according to patients' characteristics, which can be easily applied in every day clinical practice. • Glucagon-like peptide-1 (GLP-1) receptor agonists mimic the action of the endogenous GLP-1 incretin hormone, improving glycaemic control in type 2 diabetes mellitus (T2DM) by increasing insulin secretion and decreasing glucagon secretion in a glucose-dependent manner. • However, as cardiovascular (CV) morbidity and mortality is common in patients with T2DM, several trials with the use of GLP-1 receptor agonists (RAs) have been performed focusing on endpoints related to cardiovascular disease rather than metabolic control of T2DM. • Following the positive cardiovascular effects of liraglutide, dulaglutide and semaglutide observed in these trials, major changes in T2DM management guidelines have occurred. • This document from a Eastern and Southern European Diabetes Expert Group discusses the results of GLP-1 RA CV outcomes trials, their impact on recent clinical guidelines for the management of T2DM, and some selected combination regimens utilising GLP-1 RAs. • We also propose an algorithm for guiding GLP-1 RA-based treatment according to patients' characteristics, which can be easily applied in every day clinical practice. [ABSTRACT FROM AUTHOR]

(1) Background: C1q TNF-related protein 3 (CTRP3) is an adipokine with anti-inflammatory and cardioprotective properties. In our study, we explored changes in serum CTRP3 and its gene expression in epicardial (EAT) and subcutaneous (SAT) adipose tissue in patients with and without coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) undergoing elective cardiac surgery. (2) Methods: SAT, EAT, and blood samples were collected at the start and end of surgery from 34 patients: (i) 11 without CAD or T2DM, (ii) 14 with CAD and without T2DM, and (iii) 9 with both CAD and T2DM. mRNA levels of CTRP3 were assessed by quantitative reverse transcription PCR. Circulating levels of CTRP3 and other factors were measured using ELISA and Luminex Multiplex commercial kits. (3) Results: Baseline plasma levels of TNF-α and IL6 did not differ among the groups and increased at the end of surgery. Baseline circulating levels of CTRP3 did not differ among the groups and decreased after surgery. In contrast, baseline CTRP3 mRNA levels in EAT were significantly decreased in CAD/T2DM group, while no differences were found for TNF-α and IL6 gene expression. (4) Conclusions: Our data suggest that decreased EAT mRNA levels of CTRP3 could contribute to higher risk of atherosclerosis in patients with CAD and T2DM. [ABSTRACT FROM AUTHOR]

The article presents the discussion on worldwide pandemic of type 2 diabetes (T2D) and obesity. Topics include duodenal-jejunal bypass liner being developed to mimic the proposed small-bowel mechanisms of Roux-en-Y gastric bypass; and decrease in medication dosages and/or discontinuation of antidiabetes medication such as insulin being a recognized benefit of EndoBarrier treatment .

Background: Adiponectin, adipocyte fatty acid-binding protein (A-FABP), and fibroblast growth factor-19 (FGF-19) belong to proteins involved in glucose metabolism regulation. The aims of the study were to compare the plasma levels of these proteins in women with early diagnosed gestational diabetes mellitus (GDM) to those in healthy controls and to investigate their changes during pregnancy after early intervention. Methods: The study was undertaken as a case-control study. Early GDM diagnosis was based on repeated fasting plasma glucose ≥5.1 and <7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes. Age-matched controls comprised healthy pregnant and non-pregnant women. In addition to adipokines, clinical parameters and measures of glucose control were assessed. Results: Women with GDM (n = 23) had significantly lower adiponectin and higher A-FABP levels compared to healthy pregnant (n = 29) or non-pregnant (n = 25) controls, while no significant differences in FGF-19 between the groups were found. The therapeutic intervention shifted adiponectin and A-FABP levels in GDM women towards concentrations of healthy pregnant controls. Adipokines were associated with visceral adiposity and glucose control. Conclusion: Women with GDM showed altered adipokine production even in the first trimester of pregnancy. Early therapeutic intervention not only improved glucose control but also normalized impaired adipokine production. [ABSTRACT FROM AUTHOR]

Gangliosides are sialic acid-containing glycosphingolipids that are present on all mammalian plasma membranes where they participate in recognition and signaling activities. We have established mutant mice that lack GM3 synthase (CMP-NeuAc:lactosylceramide α2,3-sialyltransferase; EC 2.4.99.-). These mutant mice were unable to synthesize GM3 ganglioside, a simple and widely distributed glycosphingolipid. The mutant mice were viable and appeared without major abnormalities but showed a heightened sensitivity to insulin. A basis for the increased insulin sensitivity in the mutant mice was found to be enhanced insulin receptor phosphorylation in skeletal muscle. Importantly, the mutant mice were protected from high-fat diet-induced insulin resistance. Our results show that GM3 ganglioside is a negative regulator of insulin signaling, making it a potential therapeutic target in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Diabetes represents the leading risk factor for the development of cardiovascular disease (CVD). Chronic hyperglycemia and/or acute post-prandial changes in blood glucose determine an increase in reactive oxygen species (ROS), which play a fundamental role in endothelial dysfunction and in the nuclear transport of pro-atherogenic transcription factors that activate the "inflammasome". In addition, the glycemic alteration favors the formation and stabilization of atherosclerotic plaque through the mechanism of non-enzymatic glycation of different molecules, with the establishment of the so-called "advanced glycosylation end products" (AGE). Laboratory information provided by the level of biomarkers could make a quantitative and qualitative contribution to the clinical process of screening, prediction, prevention, diagnosis, prognosis and monitoring of cardiovascular (CV) risk linked to diabetes. This review describes the importance of specific biomarkers, with particular focus on novel ones, for stratifying and management of diabetes CV risk. [ABSTRACT FROM AUTHOR]

It is suggested that delivery whether spontaneous or by elective cesarean section is associated with an inflammatory reaction which may be modified by the type of delivery. Inflammatory reactions are associated with endothelial activation. The aim of our study was to assess endothelial biomarkers in cord and neonatal blood following different modes of delivery. The study group consisted of term healthy newborns after uncomplicated pregnancies and either spontaneous vaginal delivery (n = 39) or elective cesarean section (n = 20). Plasma soluble biomarkers were measured using multiplex magnetic bead immunoassay. The microvesicle count and number of surface antigen-specific microvesicles were determined by flow cytometry. We found significantly increased concentrations of cord blood endothelial markers (sVEGFR1, Endothelin-1 and sVCAM1) and microvesicles (EPCR/CD201+, ICAM1/CD54+ and PECAM1/CD31+) in spontaneous vaginal delivery when compared to elective cesarean section. Irrespective of the delivery mode endothelial markers sVEGFR1, Endocan, Angiopoietin-2, VEGF, and sICAM1, were significantly increased in neonatal compared to cord blood. We found increased cord blood concentrations of endothelial markers and microvesicles following spontaneous vaginal delivery, which may reflect the natural activation of endothelial cells during labor. Following the delivery, most of the soluble markers increased, as a possible consequence of activation of neonatal innate immunity and postnatal cardiovascular transition. [ABSTRACT FROM AUTHOR]

Abstract: Changes in endocrine function of adipose tissue during surgery, such as excessive production of proinflammatory cytokines, can significantly alter metabolic response to surgery and worsen its outcomes and prognosis of patients. Therapeutic hypothermia has been used to prevent damage connected with perioperative ischemia and hypoperfusion. The aim of our study was to explore the influence of deep hypothermia on systemic and local inflammation, adipose tissue hypoxia and adipocytokine production. We compared serum concentrations of proinflammatory markers (CRP, IL-6, IL-8, sIL-2R, sTNFRI, PCT) and mRNA expression of selected genes involved in inflammatory reactions (IL-6, TNF-α, MCP-1, MIF) and adaptation to hypoxia and oxidative stress (HIF1-α, MT3, GLUT1, IRS1, GPX1, BCL-2) in subcutaneous and visceral adipose tissue and in isolated adipocytes of patients undergoing cardiosurgical operation with hypothermic period. Deep hypothermia significantly delayed the onset of surgery-related systemic inflammatory response. The relative gene expression of the studied genes was not altered during the hypothermic period, but was significantly changed in six out of ten studied genes (IL-6, MCP-1, TNF-α, HIF1-α, GLUT1, GPX1) at the end of surgery. Our results show that deep hypothermia suppresses the development of systemic inflammatory response, delays the onset of local adipose tissue inflammation and thus may protect against excessive expression of proinflammatory and hypoxia-related factors in patients undergoing elective cardiac surgery procedure. [Copyright &y& Elsevier]

Abstract: Objective: The number of patients with end-stage renal disease (ESRD) is rising and these patients are at higher risk of cardiovascular disease. We studied the role of hormonal production of adipose tissue in the development of chronic inflammation in patients with ESRD before kidney transplantation. Methods: Fifteen women with ESRD and 17 healthy women (control) underwent single blood drawing and visceral and subcutaneous adipose tissue sampling during surgery (kidney transplantation in the ESRD group or cholecystectomy in the control group). Serum concentrations of C-reactive protein, interleukin-6, tumor necrosis factor-α, leptin, adiponectin, resistin, monocyte chemoattractant protein-1 were measured. Messenger RNA expression of the same hormones, adiponectin receptors 1 and 2 and immunocompetent cell marker CD68 in subcutaneous and visceral samples were measured using real-time polymerase chain reaction. Adipose tissue was examined immunohistochemically for CD68-positive cells. Results: Serum concentrations of C-reactive protein, adiponectin, resistin, interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 were significantly higher in the ESRD versus control group. Subcutaneous and visceral mRNA expressions of tumor necrosis factor-α and CD68 were significantly increased in the ESRD versus control group. Adiponectin receptor-1 and monocyte chemoattractant protein-1 mRNA expressions were significantly higher in visceral but not in subcutaneous adipose tissue of the ESRD group. Messenger RNA expressions of resistin, leptin, adiponectin, interleukin-6, and adiponectin receptor-2 in both fat depots did not significantly differ between groups. Increased infiltration of subcutaneous and visceral adipose tissue with CD68-positive immunocompetent cells was found in the ESRD group by histologic examination. Conclusion: Subcutaneous and visceral adipose tissues in ESRD express higher amounts of proinflammatory cytokines and may play a role in the development of systemic inflammation. [Copyright &y& Elsevier]