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1.
The Metabolic Syndrome: Emerging Novel Insights Regarding the Relationship between the Homeostasis Model Assessment of Insulin Resistance and other Key Predictive Markers in Young Adults of Western Algeria.
Belhayara, MI, Mellouk, Z, Hamdaoui, MS, Bachaoui, M, Kheroua, O, Malaisse, WJ
Nutrients. 2020;(3)
Abstract
Several biological markers have been identified as risk factors for cardiovascular disease and are associated with increased risk of metabolic syndrome (MetS). This study provides a factual information on promising biomarkers that are associated with MetS and can aid in early detection and management of MetS in young adults of Western Algeria. We studied a total of one hundred subjects aged between thirty and forty years with MetS, in which anthropometric measurements, insulin resistance, C peptide and HbA1c, lipid profile, circulating adipokines and glucagon-like peptide-1 were measured by suitable methods, in comparison to two groups of control. MetS is closely linked to altered glucose homeostasis, the plasma insulin/glucose ratio; i.e., the insulinogenic index helps to estimate the level of insulin secretion and also for assessing β-cell function. The correlation between homeostasis model assessment insulin resistance index (HOMA-IR) and HbA1c, body mass index or plasma triglycerides yielded positive and significant values. Biomarkers with a known and predictable association with MetS can provide a means to detect those at risk and intervene as needed. This could significantly decrease the burden complications impose on patients and the healthcare system.
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2.
Association of fasting glucagon-like peptide-1 with oxidative stress and subclinical atherosclerosis in type 2 diabetes.
Alharby, H, Abdelati, T, Rizk, M, Youssef, E, Gaber, N, Moghazy, K, Yafei, S
Diabetes & metabolic syndrome. 2019;(2):1077-1080
Abstract
AIM: Glucagon-like peptide-1(GLP-1) is a gut hormone that beside its main function in glucose homeostasis may play a role as an anti-oxidant and anti-atherosclerotic factor. The aim of this study was to estimate fasting total GLP-1 level in type 2 diabetes (T2DM) patients and to determine its relation with oxidative stress and atherosclerotic vascular changes. METHODS The study included 60 T2DM male patients with age ≥40 and 30 healthy male subjects matched for age. All of them were subjected to measuring of fasting total GLP-1, 8-iso prostaglandin F2α (8-iso PGF2α) as a marker of oxidative stress and carotid intima media thickness (CIMT) as a marker of subclinical atherosclerosis. RESULTS Fasting total GLP-1 was not significantly different in diabetics in comparison with healthy subjects (p = 0.52). Fasting total GLP-1 was found to have significant negative correlations with both 8-iso PGF2α (p < 0.05) and CIMT (p < 0.001). CONCLUSION Endogenous fasting GLP-1 appears to have anti-oxidant and anti-atherosclerotic effects in T2DM.
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3.
Glucagon like peptide-1 (GLP-1) likes Alzheimer's disease.
Yildirim Simsir, I, Soyaltin, UE, Cetinkalp, S
Diabetes & metabolic syndrome. 2018;(3):469-475
Abstract
Glucagon-like peptide-1 (GLP-1) is a 30 amino acid long peptide hormone derived from the proglucagon gene and secreted in the distal small intestine when food enters the duodenum. GLP-1 is also produced in the central nervous system (CNS), predominantly in the brainstem, and subsequently transported to a large number of regions in the CNS. Neuronal cells in nucleus tractus solitarius (NTS) can synthesize GLP-1 and extends to hypothalamus, some thalamic and cortical areas. A G protein coupled receptor (GPCR) provides the majority of GLP-1 actions. GLP-1 receptor activation triggers some in vivo signaling pathways. GLP-1 receptor agonists (GLP-1 RA) are used in the treatment diabetes and obesity. GLP-1 stimulates insulin secretion, inhibits glucagon secretion, decreases food intake, reduces appetite, delays gastric emptying, provides weight reduction, and protects β cells from apoptosis. Alzheimer's disease (AD) is the most prevalent form of dementia. It is characterized by cognitive insufficiencies and behavioral changes that impact memory and learning abilities, daily functioning and quality of life. Hyperinsulinemia and insulin resistance, which are known as pathophysiological features of the T2DM, have also been demonstrated to have significant impact on cognitive impairment. It is thought that GLP-1 affects neurological and cognitive functions, as well as its regulatory effect on glucose metabolism. The pathophysiological relationship between GLP-1 and AD is discussed in this review.
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4.
Influence of Diet and Gender on Plasma DPP4 Activity and GLP-1 in Patients with Metabolic Syndrome: An Experimental Pilot Study.
Pérez-Durillo, FT, Segarra, AB, Villarejo, AB, Ramírez-Sánchez, M, Prieto, I
Molecules (Basel, Switzerland). 2018;(7)
Abstract
Glucagon-Like Peptide-1 (GLP-1) is hydrolyzed by Dipeptidyl-Peptidase 4 (DPP4), and several studies suggest that both GLP-1 and DPP4 inhibitors have potentially beneficial effects on cardiovascular risks. The objective of this study was to analyze the differences between plasma GLP-1 and DPP4 activity in male and female patients with metabolic syndrome, and its relationship with physiological and metabolic parameters. The study included 25 apparently healthy Controls (C) and 21 Metabolic Syndrome patients (MS). Anthropometric indices, cardiovascular risk-score, and Mediterranean Diet Adherence (AMeDit) were evaluated. Fasting glucose, glycosylated hemoglobin (HbA1c), and insulin were measured. Insulin, GLP-1, and plasma DPP4 were determined within the first 30-min postprandial period. Body-Mass-Index was significantly higher, and AMeDit was significantly lower, but only in MS women. However, fasting glucose, HbA1c, and postprandial insulin were significantly higher in MS men, but not in MS women. Postprandial GLP-1 levels were lower in C men than in C women. Interestingly, in comparison with controls, we found significant lower levels of plasma DPP4 in MS-women only. Moreover, negative lineal regressions were established between DPP4 activity with waist-to-hip ratio and cardiovascular risk-score, and positive lineal regression with AMeDit. These results indicate gender differences in the behavior of GLP-1 and DPP4 activity in MS, which could be relevant for its treatment with GLP-1 analogues and DPP4 inhibitors.
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5.
Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial.
Biemann, R, Penner, M, Borucki, K, Westphal, S, Luley, C, Rönicke, R, Biemann, K, Weikert, C, Lux, A, Goncharenko, N, et al
Scientific reports. 2016;:30173
Abstract
Bile acids (BAs) are increasingly recognised as metabolic regulators, potentially improving insulin sensitivity following bariatric surgery. However, physiological relevance of such observations remains unknown. Hence, we analysed serum BA composition and associated gut-derived hormone levels following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). 74 non-smoking men (45-55 yr) with MetS were randomised to a lifestyle-induced weight loss program (supervision via telemonitoring) or to a control arm. Before and after a 6 months intervention period clinical and laboratory parameters, body composition, serum BA profile, FGF-19, and GLP-1 concentrations were determined in fasting blood samples. 30 participants in the control and 33 participants in the treatment arm completed the study and were included in the data analysis. In participants of the treatment arm lifestyle-induced weight loss resulted in markedly improved insulin sensitivity. Serum levels of BA species and total GLP-1 decreased, while FGF-19 remained stable. Serum BA composition changed towards an increased 12α-hydroxylated/non-12α-hydroxylated ratio. None of these parameters changed in participants of the control arm. Our results demonstrate that improved metabolic control by lifestyle modifications lowers serum levels of BAs and GLP-1 and changes serum BA composition towards an increased 12α/non-12α ratio (ICTRP Trial Number: U1111-1158-3672).
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6.
Insulin resistance, postprandial GLP-1 and adaptive immunity are the main predictors of NAFLD in a homogeneous population at high cardiovascular risk.
Bozzetto, L, Annuzzi, G, Ragucci, M, Di Donato, O, Della Pepa, G, Della Corte, G, Griffo, E, Anniballi, G, Giacco, A, Mancini, M, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2016;(7):623-629
Abstract
BACKGROUND AND AIMS The role of the different factors associated with fatty liver is still poorly defined. We evaluated the relationships between liver fat content (LF) and metabolic, inflammatory and nutritional factors in a homogeneous cohort of individuals at high cardio-metabolic risk. METHODS AND RESULTS In 70 individuals with high waist circumference and at least one more criterion for metabolic syndrome enrolled in a nutritional intervention study, LF was evaluated at baseline by hepatic/renal echo intensity ratio (H/R), together with dietary habits (7-day dietary record), insulin sensitivity and β-cell function (fasting and OGTT-derived indices), fasting and postprandial plasma GLP-1 and lipoproteins, and plasma inflammatory markers. H/R correlated positively with fasting and OGTT plasma glucose and insulin concentrations, HOMA-IR and β-cell function, and IL-4, IL-17, IFN-γ, TNF-α, FGF and GCSF plasma concentrations (p < 0.05 for all), and negatively with insulin sensitivity (OGIS), dietary, polyphenols and fiber (p < 0.05 for all). By multiple stepwise regression analysis, the best predictors of H/R were OGIS (β = -0.352 p = 0.001), postprandial GLP-1 (β = -0.344; p = 0.001), HDL-cholesterol (β = -0.323; p = 0.002) and IFN-γ (β = 0.205; p = 0.036). CONCLUSION A comprehensive evaluation of factors associated with liver fat, in a homogeneous population at high cardio-metabolic risk, indicated a pathogenic combination of the same pathways underlying the atherosclerotic process, namely whole body insulin sensitivity and inflammation. The higher predictive value of postprandial variables suggests that liver fat is essentially a postprandial phenomenon, with a relevant role possibly played by GLP-1. REGISTRATION NUMBER FOR CLINICAL TRIALS NCT01154478.
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7.
Specific inhibition of bile acid transport alters plasma lipids and GLP-1.
Rudling, M, Camilleri, M, Graffner, H, Holst, JJ, Rikner, L
BMC cardiovascular disorders. 2015;:75
Abstract
BACKGROUND Elobixibat is a minimally absorbed ileal bile acid (BA) transporter (IBAT) inhibitor in development against chronic constipation (CC) and constipation-predominant Irritable Bowel Syndrome (IBS-C). CC is associated with an increased risk for cardiovascular disease and type2 diabetes mellitus. The objectives of this study were to evaluate metabolic effects of elobixibat. Effects on plasma lipids and BA synthesis were evaluated utilizing a 4-week, placebo-controlled study in patients with dyslipidemia while changes of glucagon-like peptide-1 (GLP-1) by elobixibat was assayed in samples from a 14 day high-dose elobixibat study in patients with CC. METHODS Thirty-six dyslipidemic patients, 21 females, mean age 63 years, were randomized to 2.5 mg or 5 mg elobixibat or placebo once daily for four weeks. The primary endpoint was the change in low density lipoprotein (LDL) cholesterol. Secondary endpoints included other lipid parameters and serum 7α-hydroxy-4-cholesten-3-one (C4), a marker of BA (bile acid) synthesis. Another study, in 36 patients with CC treated with high dose elobixibat; 15 mg or 20 mg/day or placebo for 14 days, was evaluated for changes in GLP-1. RESULTS In the dyslipidemia study LDL cholesterol was reduced by 7.4 % (p = 0.044), and the LDL/HDL ratio was decreased by 18 % (p = 0.004). Serum C4 increased, indicating that BA synthesis was induced. No serious adverse events were recorded. In the CC study, GLP-1 increased significantly in both the 15 mg (20.7 ± 2.4 pmol/L; p = 0.03) and the 20 mg group (25.6 ± 4.9 pmol/L; p = 0.02). CONCLUSIONS Elobixibat reduces LDL cholesterol and LDL/HDL ratio and increase circulating peak GLP-1 levels, the latter in line with increased intestinal BA mediated responses in humans. TRIAL REGISTRATIONS ClinicalTrial.gov: NCT01069783 and NCT01038687 .
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8.
Gut hormones in the treatment of short-bowel syndrome and intestinal failure.
Jeppesen, PB
Current opinion in endocrinology, diabetes, and obesity. 2015;(1):14-20
Abstract
PURPOSE OF REVIEW The approval of teduglutide, a recombinant analog of human glucagon-like peptide (GLP) 2, by the US Food and Drug Administration (Gattex) and the European Medicines Agency (Revestive) has illustrated the potential of selected gut hormones as treatments in patients with short-bowel syndrome and intestinal failure. Gut hormones may improve the structural and functional intestinal adaptation following intestinal resection by decreasing a rapid gastric emptying and hypersecretion, by increasing the intestinal blood flow, and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 teduglutide studies, and pilot studies employing GLP-1 and agonists for this orphan condition. RECENT FINDINGS In a 3-week, phase 2, metabolic balance study, teduglutide increased the intestinal wet weight absorption by approximately 700 g/day and reduced fecal energy losses by approximately 0.8 MJ/day (∼200 Kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Adverse events were mainly of gastrointestinal origin and consistent with the known mechanism of action of teduglutide. Pilot studies suggest that GLP-1 may be less potent. Synergistic effects may be seen by co-treatment with GLP-2. SUMMARY Gut hormones promote intestinal adaptation and absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. This will aid the intestinal rehabilitation in these severely disabled short-bowel syndrome patients.
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9.
Gastrointestinal hormone secretion in women with polycystic ovary syndrome: an observational study.
Lin, T, Li, S, Xu, H, Zhou, H, Feng, R, Liu, W, Sun, Y, Ma, J
Human reproduction (Oxford, England). 2015;(11):2639-44
Abstract
STUDY QUESTION Is the secretion of gastrointestinal hormones impaired in patients with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Gastrointestinal hormone levels were abnormal in patients with PCOS. WHAT IS KNOWN ALREADY The hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) are both involved in signaling satiety. Secretion of GLP-1 and PYY in response to nutrients in the small intestine plays an important role in energy metabolism. Most PCOS patients are overweight or obese, which suggests dysregulation of appetite. STUDY DESIGN, SIZE, DURATION In order to evaluate levels of gastrointestinal hormones in PCOS, a cohort study was undertaken, involving 30 PCOS patients and 29 BMI-matched healthy women recruited from Shanghai Renji Hospital between 1 March 2013 and 30 May 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS After an overnight fast, all participants underwent an oral glucose tolerance test. Blood was sampled frequently for measurement of blood glucose and plasma insulin, total GLP-1 and PYY concentrations. MAIN RESULTS AND THE ROLE OF CHANCE Fasting and postprandial insulin levels were significantly higher in patients with PCOS compared with the healthy controls (P < 0.05). Fasting and postprandial GLP-1 (t = 0 and 30 min; mean ± SEM) were also higher in PCOS group (17.5 ± 1.07 pM versus 14.1 ± 1.16 pM, P < 0.05; 29.7 ± 2.39 pM versus 22.8 ± 2.09 pM, P < 0.05). However, there were no differences in plasma PYY between patients with PCOS and healthy controls either fasting or postprandially. PYY levels were lower in obese PCOS patients than in lean PCOS patients (P < 0.05). LIMITATIONS, REASONS FOR CAUTION The study involved a small number of subjects with PCOS, and examined hormone responses to oral glucose rather than a physiological meal. WIDER IMPLICATIONS OF THE FINDINGS Deficient secretion of GLP-1 and PYY does not contribute to excessive food intake in the pathophysiology of PCOS.
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10.
Gastrointestinal hormones and polycystic ovary syndrome.
Ma, J, Lin, TC, Liu, W
Endocrine. 2014;(3):668-78
Abstract
Polycystic ovary syndrome (PCOS) is an endocrine disease of women in reproductive age. It is characterized by anovulation and hyperandrogenism. Most often patients with PCOS have metabolic abnormalities such as dyslipidemia, insulin resistance, and glucose intolerance. It is not surprising that obesity is high prevalent in PCOS. Over 60 % of PCOS women are obese or overweight. Modulation of appetite and energy intake is essential to maintain energy balance and body weight. The gastrointestinal tract, where nutrients are digested and absorbed, plays a central role in energy homeostasis. The signals from the gastrointestinal tract arise from the stomach (ghrelin release), proximal small intestine (CCK release), and distal small intestine (GLP-1 and PYY) in response to food. These hormones are recognized as "appetite regulatory hormones." Weight loss is the key in the treatments of obese/overweight patients with PCOS. However, current non-pharmacologic management of body weight is hard to achieve. This review highlighted the gastrointestinal hormones, and discussed the potential strategies aimed at modifying hormones for treatment in PCOS.