-
1.
Incretin hormones, insulin, glucagon and advanced glycation end products in relation to cognitive function in older people with and without diabetes, a population-based study.
Dybjer, E, Engström, G, Helmer, C, Nägga, K, Rorsman, P, Nilsson, PM
Diabetic medicine : a journal of the British Diabetic Association. 2020;(7):1157-1166
-
-
Free full text
-
Abstract
AIM: The aim of this observational study was to investigate relationships between physiological levels of glucometabolic biomarkers and cognitive test results in a population-based setting. METHODS Cross-sectional data were obtained from the Swedish population-based Malmö Diet and Cancer Study Re-examination 2007-2012 comprising 3001 older people (mean age 72 years). Through oral glucose tolerance testing (OGTT), fasting and post-load levels of serum insulin, plasma glucagon, serum glucose-dependent insulinotropic peptide (GIP) and plasma glucagon-like peptide-1 (GLP-1) were measured. Insulin resistance and insulin sensitivity levels were calculated. In 454 participants, advanced glycation end products (AGEs) were estimated through skin autofluorescence. Associations between biomarkers and two cognitive tests, the Mini-Mental State Examination (MMSE) and A Quick Test of Cognitive Speed (AQT) respectively, were explored in multiple regression analyses. RESULTS Positive associations following adjustments for known prognostic factors were found between MMSE scores and insulin sensitivity (B = 0.822, P = 0.004), 2-h plasma glucagon (B = 0.596, P = 0.026), 2-h serum GIP (B = 0.581, P = 0.040) and 2-h plasma GLP-1 (B = 0.585, P = 0.038), whereas negative associations were found between MMSE scores and insulin resistance (B = -0.734, P = 0.006), fasting plasma GLP-1 (B = -0.544, P = 0.033) and AGEs (B = -1.459, P = 0.030) were found. CONCLUSIONS Higher levels of insulin sensitivity, GIP and GLP-1 were associated with better cognitive outcomes, but AGEs were associated with worse outcomes, supporting evidence from preclinical studies. Glucagon was linked to better outcomes, which could possibly reflect neuroprotective properties similar to the related biomarker GLP-1 which has similar intracellular properties. Longitudinal and interventional studies are needed to further evaluate neuromodulating effects of these biomarkers. Abstract presented at the European Association for the Study of Diabetes (EASD) 2019, Barcelona, Spain.
-
2.
GLP-1 and insulin regulation of skeletal and cardiac muscle microvascular perfusion in type 2 diabetes.
Love, KM, Liu, J, Regensteiner, JG, Reusch, JEB, Liu, Z
Journal of diabetes. 2020;(7):488-498
-
-
Free full text
-
Abstract
Muscle microvasculature critically regulates skeletal and cardiac muscle health and function. It provides endothelial surface area for substrate exchange between the plasma compartment and the muscle interstitium. Insulin fine-tunes muscle microvascular perfusion to regulate its own action in muscle and oxygen and nutrient supplies to muscle. Specifically, insulin increases muscle microvascular perfusion, which results in increased delivery of insulin to the capillaries that bathe the muscle cells and then facilitate its own transendothelial transport to reach the muscle interstitium. In type 2 diabetes, muscle microvascular responses to insulin are blunted and there is capillary rarefaction. Both loss of capillary density and decreased insulin-mediated capillary recruitment contribute to a decreased endothelial surface area available for substrate exchange. Vasculature expresses abundant glucagon-like peptide 1 (GLP-1) receptors. GLP-1, in addition to its well-characterized glycemic actions, improves endothelial function, increases muscle microvascular perfusion, and stimulates angiogenesis. Importantly, these actions are preserved in the insulin resistant states. Thus, treatment of insulin resistant patients with GLP-1 receptor agonists may improve skeletal and cardiac muscle microvascular perfusion and increase muscle capillarization, leading to improved delivery of oxygen, nutrients, and hormones such as insulin to the myocytes. These actions of GLP-1 impact skeletal and cardiac muscle function and systems biology such as functional exercise capacity. Preclinical studies and clinical trials involving the use of GLP-1 receptor agonists have shown salutary cardiovascular effects and improved cardiovascular outcomes in type 2 diabetes mellitus. Future studies should further examine the different roles of GLP-1 in cardiac as well as skeletal muscle function.
-
3.
The Appetite-Suppressant and GLP-1-Stimulating Effects of Whey Proteins in Obese Subjects are Associated with Increased Circulating Levels of Specific Amino Acids.
Rigamonti, AE, Leoncini, R, De Col, A, Tamini, S, Cicolini, S, Abbruzzese, L, Cella, SG, Sartorio, A
Nutrients. 2020;(3)
Abstract
UNLABELLED The satiating effect of whey proteins depends upon their unique amino acid composition because there is no difference when comparing whey proteins or a mix of amino acids mimicking the amino acid composition of whey proteins. The specific amino acids underlying the satiating effect of whey proteins have not been investigated to date. AIMS AND METHODS The aim of the present study was to evaluate the appetite-suppressant effect of an isocaloric drink containing whey proteins or maltodextrins on appetite (satiety/hunger measured by a visual analogue scale or VAS), anorexigenic gastrointestinal peptides (circulating levels of glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine (PYY)) and amino acids (circulating levels of single, total [TAA] and branched-chain amino acids [BCAA]) in a cohort of obese female subjects (n = 8; age: 18.4 ± 3.1 years; body mass index, BMI: 39.2 ± 4.6 kg/m2). RESULTS Each drink significantly increased satiety and decreased hunger, the effects being more evident with whey proteins than maltodextrins. Similarly, circulating levels of GLP-1, PYY and amino acids (TAA, BCAA and alanine, arginine, asparagine, citrulline, glutamine, hydroxyproline, isoleucine, histidine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tyrosine, and valine) were significantly higher with whey proteins than maltodextrins. In subjects administered whey proteins (but not maltodextrins), isoleucine, leucine, lysine, methionine, phenylalanine, proline, tyrosine, and valine were significantly correlated with hunger (negatively), satiety, and GLP-1 (positively). CONCLUSIONS Eight specific amino acids (isoleucine, leucine, lysine, methionine, phenylalanine, proline, tyrosine, and valine) were implicated in the appetite-suppressant and GLP-1-stimulating effects of whey proteins, which may be mediated by their binding with nutrient-sensing receptors expressed by L cells within the gastrointestinal wall. The long-term satiating effect of whey proteins and the effectiveness of a supplementation with these amino acids (i.e., as a nutraceutical intervention) administered during body weight reduction programs need to be further investigated.
-
4.
Fasting Ghrelin and Postprandial GLP-1 Levels in Patients With Morbid Obesity and Medical Comorbidities After Sleeve Gastrectomy and One-anastomosis Gastric Bypass: A Randomized Clinical Trial.
Roushdy, A, Abdel-Razik, MA, Emile, SH, Farid, M, Elbanna, HG, Khafagy, W, Elshobaky, A
Surgical laparoscopy, endoscopy & percutaneous techniques. 2020;(1):28-35
Abstract
BACKGROUND Sleeve gastrectomy (SG) and one-anastomosis gastric bypass (OAGB) are among the commonly performed bariatric procedures. This randomized study aimed to compare SG and OAGB in terms of weight loss, improvement in comorbidities, and change in serum ghrelin and glucagon-like peptide-1 (GLP-1) levels. PATIENTS AND METHODS This was a prospective randomized trial on patients with morbid obesity associated with medical comorbidities who were randomly assigned to 1 of 2 equal groups; group I underwent SG and group II underwent OAGB. Outcome measures were percent of excess weight loss (%EWL), improvement in comorbidities, change in the venous levels of fasting ghrelin and postprandial GLP-1 at 12 months after surgery, in addition to operation time and complications. RESULTS Forty patients (38 female) of a mean age of 33.8 years and mean body mass index of 48.6 kg/m2 were included. Operation time in group II was significantly longer than in group I (86 vs. 52.87 min; P<0.001). There were 6 recorded complications (1 in group I and 5 in group II, P=0.18). The %EWL, %total weight loss, and %excess body mass index loss at 6 and 12 months postoperatively were significantly higher in group II than in group I. Both groups had similar rates of improvement in comorbidities. Group I had significantly lower ghrelin and GLP-1 levels postoperatively at 6 and 12 months, respectively, as compared with group II. CONCLUSIONS OAGB was associated with significantly higher EWL than SG. The reduction in fasting ghrelin and postprandial GLP-1 serum levels at 12 months after SG was significantly higher than that after OAGB.
-
5.
Sucralose Consumption over 2 Weeks in Healthy Subjects Does Not Modify Fasting Plasma Concentrations of Appetite-Regulating Hormones: A Randomized Clinical Trial.
Romo-Romo, A, Aguilar-Salinas, CA, López-Carrasco, MG, Guillén-Pineda, LE, Brito-Córdova, GX, Gómez-Díaz, RA, Gómez-Pérez, FJ, Almeda-Valdes, P
Journal of the Academy of Nutrition and Dietetics. 2020;(8):1295-1304
Abstract
BACKGROUND The effect of nonnutritive sweeteners on appetite is controversial. Some studies have found changes in certain appetite control hormones with sucralose intake that may be through interaction with sweet taste receptors located in the intestine. OBJECTIVE The aim of this study was to evaluate whether sucralose consumption could produce changes in fasting plasma concentrations of appetite-regulating hormones, including glucagon-like peptide 1, ghrelin, peptide tyrosine tyrosine, and leptin, and secondarily in insulin resistance. DESIGN A 2-week parallel randomized clinical trial with an additional visit conducted 1 week after dosing termination. PARTICIPANTS/SETTING Sixty healthy, normal-weight individuals, without habitual consumption of nonnutritive sweeteners were recruited from July 2015 to March 2017 in Mexico City. INTERVENTION Daily sucralose consumption at 15% of the acceptable daily intake by using commercial sachets added to food. The control group followed the same protocol without an intervention. MAIN OUTCOMES MEASURED Fasting concentrations of appetite regulating hormones before and after the intervention. Fasting glucose and insulin concentrations were measured to assess insulin resistance as a secondary outcome. STATISTICAL ANALYSIS PERFORMED Basal and final concentrations were compared using Wilcoxon matched-pairs test and Mann-Whitney U test for analysis between groups. Repeated measures analysis of variance was used to evaluate changes in the homeostasis model assessment of insulin resistance. RESULTS Sucralose was not associated with changes in any of the hormones measured. One week postintervention, an incremental change (P=0.04) in the homeostasis model assessment of insulin resistance was found in the intervention group. CONCLUSIONS Sucralose intake is not associated with changes in fasting concentrations of glucagon-like peptide 1, ghrelin, peptide tyrosine tyrosine, or leptin. An increase in the homeostasis model assessment of insulin resistance observed only at 1 week postdosing is of unknown clinical significance, if any.
-
6.
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.
-
7.
Pheochromocytoma With Adrenergic Biochemical Phenotype Shows Decreased GLP-1 Secretion and Impaired Glucose Tolerance.
Petrák, O, Klímová, J, Mráz, M, Haluzíková, D, Doležalová, RP, Kratochvílová, H, Lacinová, Z, Novák, K, Michalský, D, Waldauf, P, et al
The Journal of clinical endocrinology and metabolism. 2020;(6)
Abstract
CONTEXT Impaired glucose homeostasis is a common finding in pheochromocytoma (PHEO), especially with adrenergic phenotype. The possible contribution of incretin dysfunction to dysglycemia in PHEO patients has not been studied. OBJECTIVE To compare changes in pancreatic endocrine function and gut hormones' production during a liquid meal test before and 1 year after adrenalectomy. METHODS In a prospective study, we included 18 patients with PHEO (13 females) with adrenergic biochemical phenotype. A liquid meal test with predefined isocaloric enteral nutrition was performed to evaluate dynamic changes in pancreatic hormones and incretins. RESULTS During the meal test, insulin levels were significantly lower before adrenalectomy only in the early phase of insulin secretion, but changes in area under the curve (AUC) did not reach statistical significance (AUC = 0.07). Plasma glucagon (AUC < 0.01) and pancreatic polypeptide levels (AUC < 0.01) were suppressed in comparison with the postoperative state. Impaired response to the meal was found preoperatively for glucagon-like peptide-1 (GLP-1; AUC P < 0.05), but not glucose-dependent insulinotropic polypepide (GIP; AUC P = 0.21). No significant changes in insulin resistance indices were found, except for the homeostatic model assessment-beta index, an indicator of the function of islet β cells, which negatively correlated with plasma metanephrine (R = -0.66, P < 0.01). CONCLUSIONS Our study shows suppression of pancreatic α and β cell function and impaired GLP-1 secretion during a dynamic meal test in patients with PHEO, which is improved after its surgical treatment. These data demonstrate a novel and potentially significant interconnection between excessive catecholamine production and the secretion of glucoregulatory hormones.
-
8.
Increased oral sodium chloride intake in humans amplifies selectively postprandial GLP-1 but not GIP, CCK, and gastrin in plasma.
Asmar, A, Cramon, PK, Asmar, M, Simonsen, L, Sorensen, CM, Madsbad, S, Moro, C, Hartmann, B, Rehfeld, JF, Holst, JJ, et al
Physiological reports. 2020;(15):e14519
Abstract
Human studies have demonstrated that physiologically relevant changes in circulating glucagon-like peptide-1 (GLP-1) elicit a rapid increase in renal sodium excretion when combined with expansion of the extracellular fluid volume. Other studies support the involvement of various gastrointestinal hormones, e.g., gastrin and cholecystokinin (CCK) in a gut-kidney axis, responsible for a rapid-acting feed-forward natriuretic mechanism. This study was designed to investigate the hypothesis that the postprandial GLP-1 plasma concentration is sensitive to the sodium content in the meal. Under fixed sodium intake for 4 days prior to each experimental day, 10 lean healthy male participants were examined twice in random order after a 12-hr fasting period. Arterial blood samples were collected at 10-20-min intervals for 140 min after 75 grams of oral glucose + 6 grams of oral sodium chloride (NaCl) load versus 75 grams of glucose alone. Twenty-four-hour baseline urinary sodium excretions were similar between study days. Arterial GLP-1 levels increased during both oral glucose loads and were significantly higher at the 40-80 min period during glucose + NaCl compared to glucose alone. The postprandial arterial responses of CCK, gastrin, and glucose-dependent insulinotropic polypeptide as well as glucose, insulin, and C-peptide did not differ between the two study days. Arterial renin, aldosterone, and natriuretic peptides levels did not change within subjects or between study days. Angiotensin II levels were significantly lower at the time GLP-1 was higher (60-80 min) during glucose + NaCl. Sodium intake in addition to a glucose load selectively amplifies the postprandial GLP-1 plasma concentration. Thus, GLP-1 may be part of an acute feed-forward mechanism for natriuresis.
-
9.
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.
-
10.
Risk factor reduction in type 2 diabetes demands a multifactorial approach.
Rydén, L, Ferrannini, G, Mellbin, L
European journal of preventive cardiology. 2019;(2_suppl):81-91
Abstract
Dysglycaemia (i.e. type 2 diabetes mellitus or impaired glucose tolerance) is not only common in patients with cardiovascular disease but increases the risk for future cardiovascular complications. Hyperglycaemia, the hallmark of diabetes, has since long been considered to be the link between diabetes and cardiovascular disease. Diabetes is, however, a complex, multifactorial disorder to which, for example, insulin resistance, endothelial dysfunction and factors such as increased thrombogenicity, hypertension and dyslipidaemia contribute. Thus, treatment needs to be multifactorial and to take cardiovascular aspects into account. Life-style adjustments are, together with blood pressure, lipid and glucose control, important parts of such management. Recent trial data reveal a beneficial effect on cardiovascular prognosis and mortality of blood glucose lowering agents belonging to the classes: sodium-glucose-transporter 2 inhibitors and glucagon-like peptide 1 agonists. The precise mechanisms by which certain sodium-glucose-transporter 2 inhibitors and glucagon-like peptide receptor agonists lead to these beneficial effects are only partly understood. An important impact of the benefits of sodium-glucose-transporter 2 inhibitors is a reduction in heart failure while glucagon-like peptide receptor agonists may retard the development of atherosclerotic vascular disease or stabilising plaques. Although there has been a considerable improvement in the prognosis for people with atherosclerotic diseases over the last decades there is still a gap between those with dysglycaemia, who are at higher risk, than those without dysglycaemia. This residual risk is reasonably related to two major factors: a demand for improved management and a need for new and improved therapeutic opportunities of type 2 diabetes, both routes to an improved prognosis that are at hands. This review is a comprehensive description of the possibilities to improve the prognosis for patients with dysglycaemia by a multifactorial management according to the most recent European guidelines issued in 2019 by the European Society of Cardiology in collaboration with the European Association for the Study of Diabetes.