Incretins In Patients Research Articles

PSUN326 An Interim Analysis of Healthcare Professionals’ Gaps in Incretin Knowledge Before and After Education

Abstract Background Patients with type 2 diabetes (T2D) who have poor glycemic control are at increased risk for macrovascular and microvascular disease. The growing body of cardiovascular (CV) and renal outcomes data for newer agents such as glucagon-like peptide 1 (GLP-1) receptor agonists has shifted management approaches toward therapies that provide extra glycemic benefits in addition to glucose-lowering ability. The rapidly evolving role of these new agents and new data on the potential role of a glucose-dependent insulinotropic polypeptide (GIP) agonist/GLP-1 agonist combination agent may create confusion among healthcare professionals (HCPs) treating patients with T2D. Greater competence is needed on the actions and clinical applications of current and emerging incretin-based therapies. Therefore, Clinical Care Options (CCO) created a series of online-based microlearning modules on the topic of incretin therapy in patients with T2D and cardiometabolic comorbidities for HCPs. This ongoing program, which was supported by an unrestricted medical education grant, is providing us with rich outcomes data that characterizes HCPs’ learning and current knowledge gaps regarding the use of incretins in patients with T2D. Aim The goal of this analysis was to determine the interim educational impact as well as remaining knowledge gaps among HCPs following education on incretin therapies. This information could inform future medical education that closes knowledge gaps and arms HCPs with the tools to effectively manage patients with T2D. Methods CCO produced an online educational program on incretin therapies, released in August 2021. We used pre/post questions to mine data on HCPs’ gaps. Questions measuring HCPs’ knowledge and competence were asked at baseline ("pre") and then repeated after the education was delivered ("post"). To uncover key educational gaps, we identified questions with the lowest correct responses at baseline as well as persistence of incorrect responses post education. Interim Results HCP Demographics N = 9837; MD: 61%; RPh: 10%; NP/PA: 12%; RN: 5%; other HCP: 5%, non-HCP: 8% Baseline and Remaining Gaps Incretin-based questions with topics including GLP-1 effects on glucose homeostasis, metabolic effects of GIP/GLP-1 coagonists, and the A1C-lowering ability of tirzepatide all scored <50% at baseline. Following education, the GLP-1 effect on glucose homeostasis increased only slightly from 36% to 40%, and the metabolic effects of GIP/GLP-1 coagonists increased from 19% to 54%, indicating that HCPs still struggle with understanding the effects of these agents. Conclusions This analysis demonstrates that HCPs who care for patients with T2D have significant knowledge gaps in the effects of newer incretin agents. As guidelines are placing more emphasis on the use of newer incretin agents as first-line therapy, HCPs must have the knowledge and competence of their actions to initiate incretin therapy in the primary care setting. Comparison to a similar program with an alternative format may provide further insight. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Association between 1,5-anhydro-D-sorbitol, Insulin, and Incretins in Patients with Pre-diabetes and ST-elevation Myocardial Infarction

BACKGROUND: Prediabetes itself could be an independent predictor of such adverse cardiovascular events as myocardial infarction and ischemic stroke. Since prediabetes is linked with hyperinsulinism it could also cause fluctuations of incretins concentration. Another significant fact related to prediabetes is glycemic variability. The impact of these factors on prediabetes and acute myocardial infarction is a promising phenomenon to study.
 AIM: The study aims to estimate insulin, incretins, and glycemic variability in patients with impaired carbohydrate metabolism and acute myocardial infarction
 METHODS: The 255 prediabetes patients participated in the observational case-control study. The first group included 85 patients hospitalized for STEMI. The second group included 170 patients without STEMI. Insulin and incretins were measured using a multiplex immunological assay with XMap technology on Bioplex 3D. The high-performance liquid chromatography with mass spectrometry was used to evaluate 1,5-AG concentration. The binary logistic regression was performed to evaluate the association between studying parameters and STEMI. 
 RESULTS: The insulin secretion parameters showed higher insulin and C-peptide level in patients with STEMI. A similar trend was noted for the HOMA-IR index. Among incretin, we revealed a higher level of glucagon and reduced GLP-1 in patients with STEMI. The of 1,5-AG in STEMI patients was significantly lower than in non-STEMI patients. The logistic regression model shows that a lower plasma concentration of 1,5-AG increases the odds of STEMI in patients with prediabetes [OR 2.304 (95% CI 1.980–2.973), p = 0.018]. Reduced GLP-1 concentration also increased the odds of STEMI [OR 1.775 (95% CI 1.460-1.990), p = 0.001].
 CONCLUSION: We discovered the association between 1,5-AG, GLP-1, and STEMI in patients with prediabetes. It is designating their potential role as cardiovascular risk markers in non-diabetic patients with impaired glucose metabolism.

Effects of luseogliflozin on the secretion of islet hormones and incretins in patients with type 2 diabetes.

The insufficient activity of insulin and the hyperactivity of glucagon are responsible for glucose intolerance in patients with type 2 diabetes. Whereas sodium-glucose cotransporter-2 (SGLT2) inhibitors improve blood glucose levels in patients with type 2 diabetes, their effects on the secretion profiles of glucagon and incretins remain unclear. Therefore, to investigate the effects of the SGLT2 inhibitor luseogliflozin on metabolic and endocrine profiles, 19 outpatients with type 2 diabetes were administered luseogliflozin for 12 weeks. It is of note that all subjects were treated only with diet and exercise therapy, and we were able to investigate the effects of luseogliflozin separately from the effects of other antidiabetic agents. Body weight, body fat mass, fat-free mass, and muscle mass were significantly reduced after 12 weeks of luseogliflozin administration. Glycosylated hemoglobin significantly decreased from the baseline of 8.2% ± 0.8% to 7.3% ± 0.7% (p < 0.0001). The meal tolerance test demonstrated that luseogliflozin significantly recovered glucose tolerance, accompanied by improved insulin resistance and β-cell function, whereas glucagon secretion was unaffected. Furthermore, GLP-1 secretion was significantly increased after luseogliflozin administration. Thus, luseogliflozin improved metabolic and endocrine profiles accompanied by increased GLP-1 secretion in type 2 diabetic patients without any antidiabetic medication, but did not affect glucagon secretion.

Pancreatic cancer-derived exosomes suppress the production of GIP and GLP-1 from STC-1 cells in vitro by down-regulating the PCSK1/3

One hallmark of pancreatic cancer (PC) is the high prevalence of pancreatic cancer-associated diabetes mellitus (PC-DM), but the mechanisms remain to be elucidated. Patients with PC who are diagnosed with new-onset diabetes/prediabetes have recently been shown to display significantly lower levels of glucose-dependent insulinotropic peptide (GIP) secreted mainly by enteroendocrine cells. We hypothesized that PC-derived exosomes are responsible for the decreased levels of incretins in patients with PC-DM. In this study, exosomes were successfully isolated from PANC-1, MIA PaCa-2 and SW620 cells and characterized. Only the exosomes from MIA PaCa-2 cells (Exo-Mia) reduce the production of GIP and glucagon-like peptide-1 (GLP-1) from STC-1 cells in vitro in a concentration- and time-dependent manner. Moreover, Exo-Mia increased the levels of the Gip and proglucagon mRNAs and decreased the expression of proprotein convertase subtilisin/kexin type 1/3 (PCSK1/3), which is responsible for the post-translational processing of Gip and proglucagon. Furthermore, differentially expressed exosomal miRNAs (miR-6796-3p, miR-6763-5p, miR-4750-3p and miR-197-3p) were identified and considered to be responsible for the inhibitory effects on GIP and GLP-1 production. To further determine the approach of cancer-derived exosomes reaching enteroendocrine cells, we analyzed the uptake and distribution of exosomes in animal model. It was observed that exosomes infused into the intestinal cavity were more easily internalized by the intestinal epithelium than exosomes injected into blood. In conclusion, pancreatic cancer-derived exosomes (Exo-Mia) suppress the synthesis of GIP and GLP-1 from STC-1 cells in vitro by down-regulating the PCSK1/3. Moreover, it may be the pancreatic juice that transport cancer-derived exosomes to target cells (K and L cells) in the gut.

Incretins in patients with rheumatoid arthritis

BackgroundThe precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients.MethodsWe conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules between patients and control subjects.ResultsInsulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity Score in 28 joints with erythrocyte sedimentation rate (β coefficient 46, 95% CI 6–87, p = 0.026) and Clinical Disease Activity Index (β coefficient 7.74, 95% CI 1.29–14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with β-cell function (HOMA2 of β-cell production calculated with C-peptide) in patients but not in control subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response.ConclusionsThe incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA.

Incretin secretion and glucose metabolism in morbidly obese patients in the early and late periods after biliopancreatic diversion

To estimate the parameters of glucose metabolism and to assess the secretion of incretins in patients after biliopancreatic diversion (BPD) for morbid obesity (MO) in the early and late postoperative periods. The prospective part of the investigation included 22 patients with a body mass index of 35.8 to 68.4 kg/m2 and type 2 diabetes mellitus (T2DM). All the patients were examined before, 3 weeks and 3 months after BPD. The retrospective part covered 23 patients who were examined after BPD for MO; the postoperative period was 4.7 [2.3; 7.2] years. A control group consisted of 22 healthy, normal weight volunteers. A 75-g oral glucose tolerance test was carried out in all the groups to study the levels of glucose, immunoreactive insulin (IRI), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon at 0, 30, 60, and 120 min. T2DM patients showed improvement in glucose metabolism just 3 weeks after BPD; following 3 months, they had normalized fasting blood glucose levels (5.6 [5.0; 6.0] mmol/l). During 3 months, glycated hemoglobin decreased from 7.5 [6.6; 8.5] to 5.7 [5.3; 5.9]%. In the early period following BPD, there was an increase in basal and postprandial GLP-1 levels associated with the peak IRI concentration. In the late period after BPD, the enhanced secretion of IRI and GLP-1 persisted, which was followed by a reduction in postprandial glucose levels in 4 of the 23 patients. T2DM remission does not depend on weight loss in the early period after BPD. In this period, the significant improvement of glucose metabolic parameters in patients with obesity and T2DM is associated with elevated GLP-1 levels. The altered incretin response is a stable effect of BPD and remains in its late period.

Single-dose acarbose decreased glucose-dependent insulinotropic peptide and glucagon levels in Chinese patients with newly diagnosed type 2 diabetes mellitus after a mixed meal.

BackgroundAcarbose slows down the intestinal absorption of carbohydrates, but its effects on the secretion of incretins are still poorly known. This study aimed to examine the effects of single-dose acarbose on the secretion of incretins in patients with newly diagnosed type 2 diabetes mellitus (T2DM).MethodsIn this pilot study, twenty-three patients diagnosed with T2DM were randomly assigned to the oral glucose tolerance test (OGTT) group (n = 11) and the mixed meal test (MMT) group (n = 12). Fourteen subjects with normal OGTT were included as controls. Plasma glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) were measured at 0 (fasting), 15, 30, 60, 90, and 120 min after nutrient load. A week later, controls underwent MMT, the OGTT group underwent OGTT receiving 100 mg acarbose, and the MMT group underwent MMT receiving 100 mg acarbose. The same blood markers were measured again.ResultsNo significant difference was observed in the OGTT group before and after administering acarbose. In the MMT group, postprandial levels of glucose (P < 0.01), insulin (P < 0.01), glucagon at 15 min (P < 0.05), glucagon area under the curve (AUC) (P < 0.05), GIP levels at 30 min (P < 0.05), and GIP AUC (P < 0.05) were decreased after receiving acarbose with a mixed meal, but GLP-1 levels and GLP-1 AUC did not change.ConclusionsSingle-dose acarbose could reduce the secretion of GIP and glucagon after a mixed meal in patients with newly diagnosed T2DM. The influence of acarbose on incretin levels could be related to the types of carbohydrate being consumed.Trial registrationThis study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR-TRC-14004260, Date of Registration: 2014-01-19).

Cardiovascular effects of incretins in patients with type 1 diabetes

Cardiovascular effects of incretins in patients with type 1 diabetes

Lipid metabolism and production of incretins in patients with obesity and type 2 diabetes mellitus after biliopancreatic diversion in Hess-Marceau modification at the early stages of follow-up

Objectives: To study the lipid metabolism and secretion of GLP-1 and GIP in obese patients with type 2 diabetes before and 3 months after biliopancreatic diversion (BPD) in Hess-Marceau modification.Materials and methods: 22 patients (44 [38.0; 55.0] years) with morbid obesity (BMI of 50.1 [41.3; 53.8]) and type 2 diabetes were included in the study. Total cholesterol, LDL-C, HDL-C, TG, GLP-1, GIP were evaluated before and 3 months after BPD.Results: At 3 months after BPD there were decreases in weight by 15.8% and a reduction in total cholesterol levels and LDL-C, an increase in the number of patients with a target value of total cholesterol and LDL-C (from 4/22 (18%) to 20/22 (91%, p = 0.0001)). TG levels during the first 3 months after BPD did not change, but there was a trend to an increase in the number of patients with TG target levels (from 8/22 (32%) to 15/22 (68%, p = 0.058)). Due to the reduction of total cholesterol intake after malabsorbtive surgery, we saw a regular decrease in HDL-cholesterol. 3 months after BPD there was an increase in basal secretion of GLP-1 and GIP as compared to preoperative levels, and a strong positive association of the basal GIP with the HDL-C (r = 0,8, p = 0.007) and a strong negative association – with the atherogenic index (r = – 0,7, p = 0.009) at 3 weeks after surgery.Conclusions: The majority of patients with obesity and type 2 diabetes as early as at 3 months after BPD in the modification by Hess-Marceau achieve a significant improvement in the parameters of lipid metabolism; expect positive impact of the GIP on lipid metabolism.

Cardiovascular safety of incretin-based antidiabetic treatment - results of completed clinical trials

Several randomized, controlled clinical trials were initiated some years ago in order to evaluate the cardiovascular safety of the new antidiabetic drugs in patients with type 2 diabetes due to requirements from regulatory bodies. Four trials with incretin-based drugs (saxagliptin, alogliptin, sitagliptin and lixisenatide) have been completed so far. Based on the primary outcome endpoints of these trials no cardiovascular risks were found with incretins in patients with type 2 diabetes. As for saxagliptin, the hospitalization for heart failure was investigated as a secondary endpoint, and an increased risk was observed in the respective trial; however, this observation was widely debated later in the literature. Together with ongoing trials of other novel antihyperglycemic agents, these data will provide more robust evidence about the cardiovascular safety of incretin-based antidiabetic treatment in patients with type 2 diabetes.

Nonglycemic effects of incretins in patients with long history diabetes type 1 and chronic kidney disease

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Glucose metabolism and production of incretins in patients with obesity and type 2 diabetes mellitus after Biliopancreatic bypass surgery in the modification of Hess-Marceau the early stages of postoperative monitoring

Introduction: a significant improvement was shown in metabolic control at the early stages after BPD, which was associated with GLP-1 and was regardless of weight loss.Aim: to study the secretion of GLP-1, GIP, insulin and glucagon and their relationship to the parameters of the carbohydrate metabolism among patients with obesity and type 2 diabetes before and 3 months after BPD.Materials and Methods: the check-up involved 22 patients with obesity (BMI 50.1 [41.3; 53.8] kg/m²) and type 2 diabetes. Determined: glucose, HbA1c, insulin, glucagon, GLP-1, GIP.Results: after the surgery for weight loss of 15.8% was showed a reduction of fasting and postprandial glycemia, a reduction of AUCglucose, HbA1c, НОМА-IR and hyperinsulinemia. The secretion of GLP-1 with a peak at 30' (test with a standard breakfast) increased, AUCGLP-1 – to 1.8-fold, the basal secretion of GIP – almost 2-fold and AUCGIP – to 1.7-fold; decreased of a secretion of glucagon with a minimum at 60' and AUCglucagon. A negative correlation was revealed between GIP and glucagon, AUCglucose and AUCglucagon; a positive correlation was revealed between GLP-1 and insulin. The weight loss was accompanied by an inversely proportional increase of GLP-1.Conclusion: More than 90% of the surveyed patients achieved a satisfactory glycemic control as early as 3 months after BPD. The significant improvement of the parameters of the carbohydrate metabolism was associated with elevated levels of GLP-1 and this improvement does not depend of weight loss.

Nonglycemic effects of incretins in patients with long-term type 1 diabetes mellitus and chronic kidney disease

To investigate the nonglycemic effects of incretins in patients with type 1 diabetes mellitus (DM1) of long duration (for more than 20 years) and chronic kidney disease. Seventy-five patients with varying degrees of diabetic nephropathy (DN) and without this condition, including patients receiving renal replacement therapy with programmed hemodialysis and those who had undergone kidney transplantation were examined. The levels of phosphorus-calcium metabolic indicators (calcium, phosphorus, parathyroid hormone, vitamin D, and fibroblast growth factor 23 (FGF-23)), the cardiac damage marker atrial natriuretic peptide, the proinflammatory markers monocyte chemoattractant protein 1 (MCP-1) and C-reactive protein (CRP) and the fibrotic marker transforming growth factor-β, as well as those of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were estimated in addition to conventional examination methods. All the patients underwent cardiac multislice spiral computed tomography, by calculating the Agatston index (calcium index (CI)) reflecting the degree of coronary artery calcification. The investigation revealed no relationship of GLP-1 and GIP levels to the presence and degree of DN in the patients of the study groups. GLP-1 was noted to be inversely related to patient age, indicating the diminished secretion of this peptide in older people. There was evidence that GLP-1 positively affected blood lipid composition (total cholesterol: r=-0,320; p<0.05) and the magnitude of coronary artery calcification (CI: r=-0.308; p<0.05). GIP showed a differently directed effect on the proinflammatory factors: fibrinogen (r=-0.264; p<0.05), CRP (r=-0.626; p<0.05), and FGF-23 (r=-0.341; p<0.05). The investigation has demonstrated the nonglycemic effects of incretins that favorably affect the pathogenetic processes underlying the late complications of DM1. The findings point to the potential efficacy of incretin-based drugs in preventing and treating the late complications of DM, which necessitates the conduction of larger investigations.

Effect of the ingestion of the palm oil and glutamine in serum levels of GLP-1, PYY and glycemia in diabetes mellitus type 2 patients submitted to metabolic surgery.

BackgroundIncretins are hormones produced by the intestine and can stimulate the secretion of insulin, helping to diminish the post-prandial glycemia. The administration of an emulsion of palm oil can help in the maintenance of the weight, and can increase circulating incretins levels. Glutamine increases the concentration of incretins in diabetic people. Both can help in metabolic syndrome.AimTo analyze the effects of ingestion of palm oil and glutamine in glycemia and in incretins in patients with diabetes submitted to surgical duodenojejunal exclusion with ileal interposition without gastrectomy.MethodsEleven diabetic type 2 patients were included and were operated. They were called to laboratory follow-up without eating anything between eight and 12 hours. They had there blood collected after the stimulus of the palm oil and glutamine taken in different days. For the hormonal doses were used ELISA kits.ResultsThe glycemia showed a meaningful fall between the fast and two hours after the stimulus of the palm oil (p=0,018). With the glutamine the GLP-1 showed an increase between the fast and one hour (p=0,32), the PYY showed an important increase between the fast and one hour after the stimulus (p=0,06), the glycemia showed a meaningful fall after two hours of the administration of the stimulus (p=0,03).ConclusionPalm oil and glutamine can influence intestinal peptides and glucose