Is there a justification for classifying GLP-1 receptor agonists as basal and prandial?

Altres ajuts: IM has received consultancy fess or lecture honoraria from Boerhinger Ingelheim, Eli Lilly, MSD, Novo Nordisk, Sanofi-Aventis and Astra-Zeneca and has participated in clinical trials funded by Sanofi-Aventis. AP has received consultancy fess or lecture honoraria from GSK, Boerhinger Ingelheim, Eli Lilly, Menarini, Merk, MSD, Novartis, Novo Nordisk, Pfizer, Sanofi-Aventis, AstraZeneca, Almirall and Esteve and has participated in clinical trials funded by GSK, Sanofi-Aventis, Almirall, Esteve.Several GLP-1 receptor agonists are currently available for treatment of type 2 diabetic patients. Based on their pharmacokinetic/pharmacodynamic profile, these drugs are classified as short-acting GLP-1 receptor agonists (exenatide and lixisenatide) or long-acting GLP-1 receptor agonists (exenatide-LAR, liraglutide, albiglutide, and dulaglutide). In clinical practice, they are also classified as basal or prandial GLP-1 receptor agonists to differentiate between patients who would benefit more from one or another based on characteristics such as previous treatment and the predominance of fasting or postprandial hyperglycemia. In the present article we examine available data on the pharmacokinetic characteristics of the various GLP-1 agonists and compare their effects with respect to the main parameters used to evaluate glycemic control. The article also analyzes whether the differences between the different GLP-1 agonists justify their classification as basal or prandial

PCSK9 plasma concentration is associated with epicardial adipose tissue volume and metabolic control in patients with type 1 diabetes

Cardiometabolic traits; Cardiovascular disease risk; Type 1 diabetesTrets cardiometabòlics; Risc de malaltia cardiovascular; Diabetis tipus 1Rasgos cardiometabólicos; Riesgo de enfermedad cardiovascular; Diabetes tipo 1Patients with type 1 diabetes (T1D) have a greater risk of cardiovascular disease. Proconvertase subtilisin-kexin 9 (PCSK9) is involved in the atherosclerosis process. This study aimed to determine the relationship between PCSK9 levels and epicardial adipose tissue (EAT) volume and cardiometabolic variables in patients with T1D. This was an observational cross-sectional study including 73 patients with T1D. Clinical, biochemical and imaging data were collected. We divided the patients into two groups according to their glycemic control and the EAT index (iEAT) percentile. We performed a correlation analysis between the collected variables and PCSK9 levels; subsequently, we performed a multiple regression analysis with the significant parameters. The mean age was 47.6 ± 8.5 years, 58.9% were men, and the BMI was 26.9 ± 4.6 kg/m2. A total of 31.5%, 49.3% and 34.2% of patients had hypertension, dyslipidemia and smoking habit, respectively. The PCSK9 concentration was 0.37 ± 0.12 mg/L, which was greater in patients with worse glycemic control (HbA1c > 7.5%), dyslipidemia and high EAT volume (iEAT > 75th percentile). The PCSK9 concentration was positively correlated with age (r = 0.259; p = 0.027), HbA1c (r = 0.300; p = 0.011), insulin dose (r = 0.275; p = 0.020), VLDL-C level (r = 0.331; p = 0.004), TG level (r = 0.328; p = 0.005), and iEAT (r = 0.438; p < 0.001). Multiple regression analysis revealed that 25% of the PCSK9 variability was explained by iEAT and HbA1c (p < 0.05). The PCSK9 concentration is associated with metabolic syndrome parameters, poor glycemic control and increased EAT volume in patients with T1D.This work was supported by FIS PI16/00471 and PI20/00334 from the Instituto de Salud Carlos III/Ministry of Health, co-financed by the European Regional Development Fund (FEDER “A way to make Europe”/“Investing in your future”) and a grant from the Sociedad Española de Diabetes (SED). CIBERDEM (CB07/08/0016) is an Instituto de Salud Carlos III Project

Vitamin D concentrations in familial combined hyperlipidemia: effects of lipid lowering treatment

BACKGROUND: Vitamin D deficiency has been linked to several cardiovascular risk factors but information regarding vitamin D concentrations in familial combined hyperlipidemia (FCHL) is lacking. Our objective was to examine vitamin D concentrations in patients with FCHL and to study the effects of lipid-lowering therapy. METHODS: We conducted a cross sectional study on 59 patients with FCHL and 48 healthy controls. We analyzed 25-hydroxyvitamin D (25(OH)D) concentrations and their association with lipid parameters, anthropometric measures, C-reactive protein and homeostasis model assessment (HOMA) index. Twenty-three patients with FCHL were also included in a longitudinal study conducted to analyze 25-hydroxyvitamin D concentrations before and after treatment for dyslipidemia. RESULTS: After adjustment for body mass index and seasonality, patients with FCHL had lower vitamin D concentrations than controls. Adjusted means (standard error of the mean (S.E.M)) for 25(OH)D according to the presence or absence of FCHL were 62.8 (3.6) nmol/L for patients with FCHL and 74.8 (4.1) nmol/L for controls (p = 0.021). In FCHL, hypovitaminosis D was associated with features of atherogenic dyslipidemia. After lipid-lowering therapy, vitamin D concentrations increased (51.0 ± 31.3 to 58.9 ± 24.6 nmol/L (P = 0.022)). However, changes in 25(OH)D concentrations did not correlate with changes in other parameters. CONCLUSIONS: Our findings suggest that FCHL is associated with decreased vitamin D concentrations and that treatment for dyslipidemia improves vitamin D status through an unknown mechanism. Further studies are needed to replicate these data in larger populations and to elucidate the mechanisms involved in this association

A novel truncated form of apolipoprotein A-I transported by dense LDL is increased in diabetic patients

Diabetic (DM) patients have exacerbated atherosclerosis and high CVD burden. Changes in lipid metabolism, lipoprotein structure, and dysfunctional HDL are characteristics of diabetes. Our aim was to investigate whether serum ApoA-I, the main protein in HDL, was biochemically modified in DM patients. By using proteomic technologies, we have identified a 26 kDa ApoA-I form in serum. MS analysis revealed this 26 kDa form as a novel truncated variant lacking amino acids 1-38, ApoA-IΔ(1-38). DM patients show a 2-fold increase in ApoA-IΔ(1-38) over nondiabetic individuals. ApoA-IΔ(1-38) is found in LDL, but not in VLDL or HDL, with an increase in LDL3 and LDL4 subfractions. To identify candidate mechanisms of ApoA-I truncation, we investigated potentially involved enzymes by in silico data mining, and tested the most probable molecule in an established animal model of diabetes. We have found increased hepatic cathepsin D activity as one of the potential proteases involved in ApoA-I truncation. Cathepsin D-cleaved ApoA-I exhibited increased LDL binding affinity and decreased antioxidant activity against LDL oxidation. In conclusion, we show for the first time: a) presence of a novel truncated ApoA-I form, ApoA-IΔ(1-38), in human serum; b) ApoA-IΔ(1-38) is transported by LDL; c) ApoA-IΔ(1-38) is increased in dense LDL fractions of DM patients; and d) cathepsin D-ApoA-I truncation may lead to ApoA-IΔ(1-38) binding to LDLs, increasing their susceptibility to oxidation and contributing to the high cardiovascular risk of DM patients. This research was originally published in Lipid Research. A novel truncated form of apolipoprotein A-I transported by dense LDL is increased in diabetic patients. Journal of Lipid Research. 2015. 56: 1762-1773 © the American Society for Biochemistry and Molecular Biology.Peer Reviewe

Familial Combined Hyperlipidemia (FCH) Patients with High Triglyceride Levels Present with Worse Lipoprotein Function Than FCH Patients with Isolated Hypercholesterolemia

Lipoprotein characteristics were analyzed in familial combined hyperlipidemia (FCH) patients before and after statin treatment. Twenty-six FCH patients were classified according to the presence (HTG group, n = 13) or absence (normotriglyceridemic (NTG) group, n = 13) of hypertriglyceridemia. Fifteen healthy subjects comprised the control group. Lipid profile, inflammation markers, and qualitative characteristics of lipoproteins were assessed. Both groups of FCH subjects showed high levels of plasma C-reactive protein (CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and apolipoprotein J. Statins reverted the increased levels of Lp-PLA2 and CRP. Lipoprotein composition alterations detected in FCH subjects were much more frequent in the HTG group, leading to dysfunctional low-density lipoproteins (LDL) and high-density lipoproteins (HDL). In the HTG group, LDL was smaller, more susceptible to oxidation, and contained more electronegative LDL (LDL(-)) compared to the NTG and control groups. Regarding HDL, the HTG group had less Lp-PLA2 activity than the NTG and control groups. HDL from both FCH groups was less anti-inflammatory than HDL from the control group. Statins increased LDL size, decreased LDL(-), and lowered Lp-PLA2 in HDL from HTG. In summary, pro-atherogenic alterations were more frequent and severe in the HTG group. Statins improved some alterations, but many remained unchanged in HTG

Assessing motivational stages and processes of change for weight management around bariatric surgery: a multicenter study

[Abstract] Introduction/purpose: The assessment of the patients' motivation as a predictor of behavioral change via five stages (pre-contemplation, contemplation, preparation, action, and maintenance) and four processes (emotional re-evaluation, weight management actions, environmental restructuring, and weight consequences evaluation) of change. Materials/methods: A total of 542 participants (251 waiting for bariatric surgery (BS), 90 undergoing BS, and 201 controls) completed the Stages (S-Weight) and Processes (P-Weight) of Change in Overweight and Obese People questionnaires in a multicenter cross-sectional study. Results: A higher percentage of subjects seeking BS (31.7%) were in the action stage (16.7% of post-BS patients, p < 0.001; 14.9% of controls, p < 0.001). The referred body mass index (BMI) reduction was higher in subjects in active stages (3.6 ± 4.4 kg/m2 in maintenance versus 1.4 ± 1.4 kg/m2 in contemplation, p < 0.001). In the P-Weight questionnaire, patients looking for BS scored significant higher in the four processes of change than controls. In addition, a positive and significantly correlation between BMI and the four processes was observed. In the stepwise multivariate analysis, BMI and the S-Weight allocation were constantly associated with the four processes of change. Conclusion: Obesity is accompanied by a modifying behavioral stage, suggesting that subjects before BS are seriously thinking about overcoming excess weight. To identify subjects on the waiting list for BS who will be more receptive to weight lost interventions remains a challenge

Hipovitaminosis D y obesidad. Relación con el grado de obesidad y el síndrome metabólico

En 343 sujetos con sobrepeso u obesidad demostramos la existencia de una relación inversa entre los niveles (r -0,403, p 40 Kg/m2. Asimismo, los pacientes con síndrome metabólico tenían niveles de calcidiol inferiores (43,35 ± 29,01 nmol/L y 55,26 ± 29,6 nmol/L) y presentaban una mayor prevalencia de hipovitaminosis D, independientemente del grado de obesidad. Estos datos sugieren, que como ocurre para otras comorbilidades asociadas con la obesidad, la distribución de la adiposidad parece desarrollar un papel en el estado de la vitamina D.En 343 subjectes amb sobrepès o obesitat demostrem l'existència d'una relació inversa entre els nivells (r -0,403, p 40 Kg/m2. A més a més, els pacients amb síndrome metabòlica tenien nivells de calcidiol inferiors (43,35 ± 29,01 nmol/L i 55,26 ± 29,6 nmol/L) i presentaven una major prevalença de d'hipovitaminosi D, independentment del grau d'obesitat. Aquestes dades suggereixen que, com succeeix amb altres comorbiditats associades a l'obesitat, la distribució del greix sembla jugar un paper en l'estat de la vitamina D

Obesity Surgery Improves Hypogonadism and Sexual Function in Men without Effects in Sperm Quality

Obesity is associated with hypogonadism, sexual dysfunction, and impaired fertility in men. However, its effects on semen parameters or sexual function remain debatable. This paper involves a longitudinal study in men submitted for obesity surgery at a university tertiary hospital. Patients were studied at baseline and at 6, 12, and 18 months after obesity surgery. At each visit, anthropometry measures were collected and hormonal and semen parameters were studied. Sexual function was evaluated with the International Index of Erectile Function (IIEF). A total of 12 patients were included. The average body mass index of patients decreased from 42.37 ± 4.44 to 29.6 ± 3.77 kg/m 2 at 18 months after surgery (p < 0.05). Hormonal parameters improved after obesity surgery. The proportion of sperm cells with normal morphology tended to decrease from baseline and became most significant at 18 months (5.83 ± 4.50 vs. 2.82 ± 2.08). No significant changes were found in the remaining semen parameters. Erectile function improved significantly at six months after surgery. The authors believe that, in general, the effects of obesity surgery on fertility may be limited or even deleterious (at least in the short and midterm follow-up)

Divergent Effects of Glycemic Control and Bariatric Surgery on Circulating Concentrations of TMAO in Newly Diagnosed T2D Patients and Morbidly Obese

High circulating concentrations of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are significantly associated with the risk of obesity and type 2 diabetes (T2D). We aimed at evaluating the impact of glycemic control and bariatric surgery on circulating concentrations of TMAO and its microbiota-dependent intermediate, γ-butyrobetaine (γBB), in newly diagnosed T2D patients and morbidly obese subjects following a within-subject design. Based on HbA1c concentrations, T2D patients achieved glycemic control. However, the plasma TMAO and γBB concentrations were significantly increased, without changes in estimated glomerular filtration rate. Bariatric surgery was very effective in reducing weight in obese subjects. Nevertheless, the surgery reduced plasma γBB concentrations without affecting TMAO concentrations and the estimated glomerular filtration rate. Considering these results, an additional experiment was carried out in male C57BL/6J mice fed a Western-type diet for twelve weeks. Neither diet-induced obesity nor insulin resistance were associated with circulating TMAO and γBB concentrations in these genetically defined mice strains. Our findings do not support that glycemic control or bariatric surgery improve the circulating concentrations of TMAO in newly diagnosed T2D and morbidly obese patients

The Association of Hypovitaminosis D with the Metabolic Syndrome Is Independent of the Degree of Obesity

Background. It remains uncertain whether the metabolic syndrome (MS) or insulin resistance contribute to the association between vitamin D deficiency and obesity. Methods. We conducted a cross-sectional survey of 343 subjects who were overweight or obese. We analyzed anthropometric data and the presence or absence of MS. Additionally, we determined 25-hydroxyvitamin D (25OHD) and insulin concentrations, and the HOMA index was calculated. Chi-square test,Mann-Whitney U test, Student's t -tests,and logistic regression analysis were used. Results. The mean age of the patients was 42 ± 11 years, and 65.9% were women. The mean BMI was 34.7 ± 8.3 kg/m 2 and 25(OH)D levels were 53.7 ± 29.8 nmol/L. Forty-six patients (13.4%) had MS. Vitamin D status was associated with the degree of obesity, especially with a BMI > 40 kg/m 2. Patients with MS had lower levels of 25(OH)D than patients without (43.3 ± 29.0 versus 55.3 ± 29.6 mmol/L, resp.), and the odds ratio for hypovitaminosis D was 2.7 (confidence interval (CI), 1.14-6.4) (P =.023) for patients with MS versus patients without MS, irrespective of the degree of obesity. Conclusions. Our data confirm the association between vitamin D and MS and suggest that this association is independent of the degree of obesity