Have a heart: failure to increase GLP-1 caused by heart failure increases the risk of diabetes

2020 ◽  
Vol 134 (23) ◽  
pp. 3119-3121
Author(s):  
Michael J. Ryan
Keyword(s):  
Heart Failure ◽  
Blood Glucose ◽  
Blood Glucose Control ◽  
Inhibitory Peptide ◽  
Glucose Lowering ◽  
Claude Bernard ◽  
Specific Fraction ◽  
Series Of Experiments ◽  
Glucagon Like Peptide 1 ◽  
Treasure Island

Abstract Incretins represent a group of gut-derived peptide hormones that, at physiological concentrations, potentiate the release of insulin. Work leading to the discovery of incretins began as early as the late 1800s where scientists, including Claude Bernard who is widely considered the father of modern physiology (Rehfeld, J.F. The Origin and Understanding of the Incretin Concept. Front. Endocrinol. (Lausanne) (2018) 9, 387; Robin, E.D. Claude Bernard. Pioneer of regulatory biology. JAMA (1979) 242, 1283–1284), attempted to understand the pancreas as an important organ in the development of diabetes mellitus and blood glucose control. After the seminal work of Paulescu and Banting and Best in the early 1920s that led to the discovery of insulin (Murray I. Paulesco and the isolation of insulin. J. Hist. Med. Allied Sci. (1971) 26, 150–157; Raju T.N. The Nobel Chronicles. 1923: Frederick G. Banting (1891–1941), John J.R. Macleod (1876–1935). Lancet (1998) 352, 1482), attention was turned toward understanding gastrointestinal factors that might regulate insulin secretion. A series of experiments by Jean La Barre showed that a specific fraction of intestinal extract caused a reduction in blood glucose. La Barre posited that the fraction’s glucose lowering actions occurred by increasing insulin release, after which he coined the term ‘incretin’. In the 1970s, the first incretin was purified, glucose insulinotropic polypeptide (GIP) (Gupta K. and Raja A. Physiology, Gastric Inhibitory Peptide StatPearls Treasure Island (FL); 2020), followed by the discovery of a second incretin in the 1980s, glucagon-like peptide-1 (GLP-1). Interest and understanding of the incretins, has grown since that time.

scholarly journals Glucose-Responsive Microneedle Patches for Diabetes Treatment

2018 ◽  
Vol 13 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Guojun Chen ◽  
Jicheng Yu ◽  
Zhen Gu
Keyword(s):  
Drug Delivery ◽  
Blood Glucose ◽  
Release Kinetics ◽  
Blood Glucose Control ◽  
Diabetes Therapy ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Treatment Of Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Antidiabetic therapeutics, including insulin as well as glucagon-like peptide 1 (GLP-1) and its analogs, are essential for people with diabetes to regulate their blood glucose levels. Nevertheless, conventional treatments based on hypodermic administration is commonly associated with poor blood glucose control, a lack of patient compliance, and a high risk of hypoglycemia. Closed-loop drug delivery strategies, also known as self-regulated administration, which can intelligently govern the drug release kinetics in response to the fluctuation in blood glucose levels, show tremendous promise in diabetes therapy. In the meantime, the advances in the development and use of microneedle (MN)-array patches for transdermal drug delivery offer an alternative method to conventional hypodermic administration. Hence, glucose-responsive MN-array patches for the treatment of diabetes have attracted increasing attentions in recent years. This review summarizes recent advances in glucose-responsive MN-array patch systems. Their opportunities and challenges for clinical translation are also discussed.

Effects of intraduodenal glucose and fructose on antropyloric motility and appetite in healthy humans

2000 ◽  
Vol 278 (2) ◽  
pp. R360-R366 ◽  
Author(s):  
C. K. Rayner ◽  
H. S. Park ◽  
J. M. Wishart ◽  
M.-F. Kong ◽  
S. M. Doran ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Food Intake ◽  
Plasma Insulin ◽  
Insulin Response ◽  
Oral Glucose ◽  
Inhibitory Peptide ◽  
Healthy Humans ◽  
Significant Difference ◽  
Glucagon Like Peptide 1 ◽  
Gip Release

Oral fructose empties from the stomach more rapidly and may suppress food intake more than oral glucose. The purpose of the study was to evaluate the effects of intraduodenal infusions of fructose and glucose on antropyloric motility and appetite. Ten healthy volunteers were given intraduodenal infusions of 25% fructose, 25% glucose, or 0.9% saline (2 ml/min for 90 min). Antropyloric pressures, blood glucose, and plasma insulin, gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) were measured concurrently; a buffet meal was offered at the end of the infusion. Intraduodenal fructose and glucose suppressed antral waves ( P < 0.0005 for both), stimulated isolated pyloric pressure waves ( P < 0.05 for both), and increased basal pyloric pressure ( P = 0.10 and P < 0.05, respectively) compared with saline, without any significant difference between them. Intraduodenal glucose increased blood glucose ( P < 0.0005), as well as plasma insulin ( P < 0.0005) and GIP ( P < 0.005) more than intraduodenal fructose, whereas there was no difference in the GLP-1 response. Intraduodenal fructose suppressed food intake compared with saline ( P < 0.05) and glucose ( P = 0.07). We conclude that, when infused intraduodenally at 2 kcal/min for 90 min 1) fructose and glucose have comparable effects on antropyloric pressures, 2) fructose tends to suppress food intake more than glucose, despite similar GLP-1 and less GIP release, and 3) GIP, rather than GLP-1, probably accounts for the greater insulin response to glucose than fructose.

Abstract 4609: Evidence of Need for a More Comprehensive Approach to Dietary Self-Management for Patients with Heart Failure and Diabetes

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Heather Payne-Emerson ◽  
Eun Kyeung Song ◽  
Seongkum Heo ◽  
Debra K Moser ◽  
Misook L Chung ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Glucose ◽  
Sodium Intake ◽  
Microvascular Complications ◽  
Fasting Blood Glucose ◽  
Blood Glucose Control ◽  
Lower Percentage ◽  
Similar Amount ◽  
Nutritional Management ◽  
Patients With Heart Failure

Background: Type 2 diabetes (DM) is a common comorbidity in patients with heart failure (HF). Nutritional management is a key strategy in achieving blood glucose control and decreasing the risk of microvascular complications. The ability of patients with HF to nutritionally self-manage multiple comorbidities is unknown. Purpose: To compare nutritional intake of a group of patients with HF and DM with a group without DM. Methods: A total of 174 patients (66 with DM, age 60± 12 yrs, 35% female, 57% NYHA class III/IV) recruited from HF clinics completed detailed 4-day food diaries that were reviewed by a registered dietitian. Nutrition Data System software was used to determine carbohydrate (total and subtype), protein, fat, cholesterol, and sodium intake. Fasting blood glucose was obtained on a subset of 123 patients. Between-group comparisons were made using independent sample t-tests. Results: Patients with DM consumed a lower percentage of calories from carbohydrate (44% vs. 49%, p=.003) and a greater percentage of calories from protein (19% vs. 16%, p<.001) and fat (38% vs. 35%, p=.049) compared to patients without DM. With respect to carbohydrate subtypes, patients with DM consumed 30% less sucrose (29g vs. 42g, p<.001) and 39% less fructose (14g vs. 23g, p<.001) than patients without DM, but a similar amount of starch (93g vs. 95g). There were no differences in sodium (3472mg vs. 3209mg), cholesterol (321mg vs. 285mg) or saturated fat (12% vs. 11% of kcal) intake between groups with and without DM. A total of 60% of patients with DM had fasting blood glucose levels >120mg/dl and 40% had a fasting levels > 140mg/dl. Conclusions: Patients with HF and DM primarily limited dietary sugar intake, with only moderate success. Nutritional management of HF has focused on the single nutrient sodium with limited success; these data suggest that teaching for DM may be similarly focused on the single nutrient sugar. This indicates that new, more comprehensive, approaches are needed to help patients meet the challenge of nutritionally managing multiple comorbidities. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).

Glucagon-like peptide-1 based therapies: Effects beyond blood glucose control

2013 ◽  
Vol 13 (5-6) ◽  
pp. 229-237
Author(s):  
Subash C Sivaraman ◽  
Thomas M Barber ◽  
Paul O’Hare ◽  
Harpal S Randeva
Keyword(s):  
Blood Glucose ◽  
Glucose Control ◽  
Blood Glucose Control ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Glycaemic Control in Diabetes

2021 ◽  
Author(s):  
D. Müller-Wieland ◽  
J. Brandts ◽  
M. Verket ◽  
N. Marx ◽  
K. Schütt
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Blood Glucose ◽  
Kidney Disease ◽  
Treatment Guidelines ◽  
Glucose Lowering ◽  
Receptor Agonists ◽  
Cardiovascular Endpoint

AbstractReduction of glucose is the hallmark of diabetes therapy proven to reduce micro- and macro-vascular risk in patients with type 1 diabetes. However glucose-lowering efficacy trials in type 2 diabetes didn’t show major cardiovascular benefit. Then, a paradigm change in the treatment of patients with type 2 diabetes has emerged due to the introduction of new blood glucose-lowering agents. Cardiovascular endpoint studies have proven HbA1c-independent cardioprotective effects for GLP-1 receptor agonists and SGLT-2 inhibitors. Furthermore, SGLT-2 inhibitors reduce the risk for heart failure and chronic kidney disease. Mechanisms for these blood glucose independent drug target-related effects are still an enigma. Recent research has shown that GLP-1 receptor agonists might have anti-inflammatory and plaque stabilising effects whereas SGLT-2 inhibitors primarily reduce pre- and after-load of the heart and increase work load efficiency of the heart. In addition, reduction of intraglomerular pressure, improved energy supply chains and water regulation appear to be major mechanisms for renoprotection by SGLT-2 inhibitors. These studies and observations have led to recent changes in clinical recommendations and treatment guidelines for type 2 diabetes. In patients with high or very high cardio-renal risk, SGLT-2 inhibitors or GLP-1 receptor agonists have a preferred recommendation independent of baseline HbA1c levels due to cardioprotection. In patients with chronic heart failure, chronic kidney disease or at respective risks SGLT-2 inhibitors are the preferred choice. Therefore, the treatment paradigm of glucose control in diabetes has changed towards using diabetes drugs with evidence-based organ protection improving clinical prognosis.

Glucose-lowering therapies in patients with type 2 diabetes and cardiovascular diseases

2019 ◽  
Vol 26 (2_suppl) ◽  
pp. 73-80 ◽  
Author(s):  
Francesco Prattichizzo ◽  
Lucia La Sala ◽  
Lars Rydén ◽  
Nikolaus Marx ◽  
Marc Ferrini ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Receptor Agonist ◽  
Glucose Lowering ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Type 2 diabetes mellitus is a major risk factor for developing cardiovascular disease, and many patients with diabetes have prevalent cardiovascular complications. Recent cardiovascular outcome clinical trials suggest that certain new glucose-lowering drugs are accompanied by additional cardioprotective properties. Indeed, selected glucagon-like peptide-1 receptor agonists have a proved cardiovascular benefit in terms of a reduced incidence of ischaemic events, while sodium/glucose co-transporter-2 inhibitors have also shown significant protection, with a striking effect on heart failure and renal endpoints. These findings have been integrated in recent guidelines which now recommend prescribing (when initial metformin monotherapy fails) a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor with clinical trial-confirmed benefit in patients with diabetes and atherosclerotic cardiovascular disease, and a sodium/glucose co-transporter-2 inhibitor in such patients with heart failure or chronic kidney disease at initial stages. Furthermore, the new 2019 European Society of Cardiology guidelines in collaboration with the European Association for the Study of Diabetes recommend a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor in treatment-naive patients with type 2 diabetes mellitus with pre-existing cardiovascular disease or at high cardiovascular risk. Future research will disentangle the mechanisms underpinning these beneficial effects and will also establish to what extent these results are generalisable to the whole diabetes population. In the meantime, available evidence should prompt a wide diffusion of these two classes of drugs among patients with diabetes and cardiovascular disease. Here, we briefly summarise recent findings emerging from cardiovascular outcome clinical trials, discuss their impact on treatment algorithms and propose new possible approaches to improve our knowledge further regarding the cardiovascular effect of glucose-lowering medications.

scholarly journals A glükagonszerű peptid-1 (GLP1) és a gyomor-bél rendszer. GLP1-receptor-agonisták – túlértékelt gyomor-, elfelejtődött bél- („ileal brake”) hatás?

2019 ◽  
Vol 160 (49) ◽  
pp. 1927-1934
Author(s):  
Gábor Winkler ◽  
Péter Hajós ◽  
János Tibor Kiss
Keyword(s):  
Blood Glucose ◽  
Bowel Function ◽  
Postprandial Blood Glucose ◽  
Pancreatic Acinar Cells ◽  
Ileal Brake ◽  
Glucose Lowering ◽  
Receptor Agonists ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Glucose Lowering Therapy

Abstract: Glucagon-like peptide-1 (GLP1) and their receptor agonists – beside their blood glucose lowering and central effects- affect also the gastrointestinal function in many respects. They slow down the stomach emptying, the motility of the small bowel and colon – this is the explanation for the “ileal brake” terminology –, stimulate the function of exocrine pancreatic acinar cells and increase amylase production. GLP1 receptor agonists belong to the defining tools of the blood glucose lowering therapy in type 2 diabetes. Their long- and short-acting derivatives have different influence on the fasting and the postprandial blood glucose, respectively. By introducing the term non-prandial and prandial type analogues – which seems to be forced in light of the newer data – the potential slowdown in gastric emptying is the center of interest, lately, however, especially in the case of long-acting GLP1 variants, at least such attention should be paid to controlling bowel function. The article reviews the physiological effects of GLP1 on the gastrointestinal tract and draws attention to the potential for the prevention of possible side effects through detailed patient information and dietary advises. Orv Hetil. 2019; 160(49): 1927–1934.

scholarly journals Effects of sub-chronic exposure to naturally occurring N-terminally truncated metabolites of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), GIP(3–42) and GLP-1(9–36)amide, on insulin secretion and glucose homeostasis in ob/ob mice

2006 ◽  
Vol 191 (1) ◽  
pp. 93-100 ◽  
Author(s):  
J C Parker ◽  
K S Lavery ◽  
N Irwin ◽  
B D Green ◽  
B Greer ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Plasma Glucose ◽  
Glucose Control ◽  
Chronic Exposure ◽  
Blood Glucose Control ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are important enteroendocrine hormones that are rapidly degraded by an ubiquitous enzyme dipeptidyl peptidase IV to yield truncated metabolites GIP(3–42) and GLP-1(9–36)amide. In this study, we investigated the effects of sub-chronic exposure to these major circulating forms of GIP and GLP-1 on blood glucose control and endocrine pancreatic function in obese diabetic (ob/ob) mice. A once daily injection of either peptide for 14 days had no effect on body weight, food intake or pancreatic insulin content or islet morphology. GLP-1(9–36)amide also had no effect on plasma glucose homeostasis or insulin secretion. Mice receiving GIP(3–42) exhibited small but significant improvements in non-fasting plasma glucose, glucose tolerance and glycaemic response to feeding. Accordingly, plasma insulin responses were unchanged suggesting that the observed enhancement of insulin sensitivity was responsible for the improvement in glycaemic control. These data indicate that sub-chronic exposure to GIP and GLP-1 metabolites does not result in physiological impairment of insulin secretion or blood glucose control. GIP(3–42) might exert an overall beneficial effect by improving insulin sensitivity through extrapancreatic action.

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