Curve For Glucagon-like Peptide-1 Research Articles

995-P: Glucagon-Like Peptide-1 (GLP-1) Levels following OGTT Mirror Insulin Resistant States (IRS) in Prediabetes Subjects: A Multi-Ethnic Comparative Study

Introduction: IRS is a precursor to the development of prediabetes which manifests itself in the form of compensatory insulin secretion. The role of GLP-1 in this compensatory mechanism has not been well studied especially among various ethnic groups.Aim: To assess differences in GLP-1 responses to OGTT and its relationship to insulin resistance indices (HOMA-IR) among 3 major ethnic groups with prediabetes.Methods: Fifty-four prediabetes subjects (21 Malays, 17 Chinese and 16 Indians) matched for age, gender, BMI and waist circumference underwent a 75-g OGTT. Plasma glucose and total GLP-1 concentrations were measured at 0, 30 and 120 minutes. Fasting glucose and insulin were obtained for the HOMA analyses.Results: Indians were the most insulin resistant. This is mirrored by Indians having the highest GLP-1 levels at 0, 30 and 120 minutes. Similarly, the area under the curve for GLP-1 was 59% higher in Indians and 50% higher in Chinese compared to the Malays. GLP-1 level was positively correlated with HOMA-IR (r=0.576, p<0.001). Ethnicity was a significant determinant of GLP-1 level with Indians exhibiting the strongest positive correlation (B=7.02, p<0.001).Conclusions: In prediabetes, GLP-1 responses post-OGTT increased proportionately to IRS, evidenced by the augmented GLP-1 responses in the Indians who possessed the highest HOMA-IR indices.View largeDownload slideView largeDownload slide DisclosureS. C. Chong: None. N. Sukor: None. S. Robert: None. K. F. Ng: None. N. A. Kamaruddin: None.FundingNational University of Malaysia Medical Centre (GUP-2017-066); Malaysian Endocrine & Metabolic Society (L12-MEMS6)

Effects of Different Immunosuppressive Drugs on Incretins in Renal Transplant Patients

BackgroundImmunosuppressive drugs used in transplantation patients, may contribute to the development of post-transplant diabetes mellitus through their possible adverse effects on incretins. We aimed to compare the effects of different immunosuppressive drugs used in renal transplantation patients on glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels. Patients and methodsForty five subjects were enrolled in the study (cyclosporine-treated 15 and tacrolimus-treated renal transplant patients 15, and healthy volunteers as a control group 15). Oral glucose tolerance test with 75 gr glucose was performed. GLP-1 and GIP levels were measured at 0 (baseline), 30, 60, 90, 120 min using ELISA method. ResultsA statistically significant level of difference was detected in GLP-1 levels at the baseline, 30th and 120th minutes among all three groups (p < 0,001, p = 0,026 and p = 0,022, respectively). Baseline GLP-1 levels in cyclosporine-treated renal transplant patients were higher than in both tacrolimus-treated renal transplant patients (p = 0,016) and control groups (p < 0,001). GLP-1 levels at the 30th minute were higher in tacrolimus-treated renal transplant patients when compared to the cyclosporine-treated renal transplant patients (p = 0,024). GLP-1 levels at the 120th minute were higher in tacrolimus-treated renal transplant patients than the control group (p = 0,024). The areas under the curve of GLP-1 was higher in tacrolimus-treated renal transplant patients when compared to the control group (p = 0,018). GIP levels at 120th was lower in cyclosporine-treated renal transplant patients when compared to control group (p = 0,003). ConclusionThese findings showed a temporally affected incretin hormones in renal transplant patients, a preserved GLP-1 response to an oral glucose load in renal transplant patients on cyclosporine and increased GLP -1 response to an oral glucose load in those on tacrolimus.

Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients

Studies in mice have shown that the intestinal microbiota can contribute to obesity via the anorexigenic gut hormone glucagon-like peptide 1 (GLP1) and bile acids, which affect lipid metabolism. We performed a randomized, placebo-controlled, pilot study of the effects of fecal microbiota transplantation (FMT) in obese, metabolically uncompromised patients. We performed a double-blind study of 22 obese patients (body mass index [BMI] ≥5 kg/m2) without a diagnosis of diabetes, nonalcoholic steatohepatitis, or metabolic syndrome. Participants were assigned randomly (1:1) to groups that received FMT by capsules (induction dose of 30 capsules at week 4 and maintenance dose of 12 capsules at week 8) or placebo capsules. FMT capsules were derived from a single lean donor (BMI, 17.5 kg/m2). Patients were followed up through week 26; the primary outcome was safety. Stool and serum samples were collected from patients at baseline and at weeks 1, 4, 6, 8, and 12 after administration of the first dose of FMT or placebo and analyzed by 16S RNA gene sequencing. Stool and serum samples were analyzed for metabolomics by liquid chromatography-mass spectrometry. Additional outcomes were the change in area under the curve for GLP1 at week12. We observed no significant differences in adverse events between patients who received FMT vs placebo. There was no increase in the area under the curve of GLP1 in either group. Patients who received FMT had sustained shifts in microbiomes associated with obesity toward those of the donor (P < .001). Patients who received FMT had a sustained decrease in stool levels of taurocholic acid (P < .05) compared with baseline; bile acid profiles began to resemble those of the donor more closely. We did not observe significant changes in mean BMI at week 12 in either group. In a placebo-controlled pilot study, we found that FMT capsules (derived from a lean donor) were safe but did not reduce BMI in obese metabolically uncompromised patients. The FMT capsules were well tolerated and led to sustained changes in the intestinal microbiome and bile acid profiles that were similar to those of the lean donor. ClinicalTrials.gov number: NCT02741518.

Change in insulin resistance, beta cell function, glucagon-like peptide-1 and calcitonin levels two weeks after bariatric surgery

Aim of the studyBariatric surgery causes profound improvement in metabolic parameters by increasing plasma glucagon like peptide - 1 (GLP-1) level even few weeks after surgery. GLP-1 analogues can cause calcitonin secreting medullary thyroid carcinoma in animals. The studies relating to the mechanisms that underlie these changes are few. The objectives of the study were to measure the change in insulin resistance, beta cell function, GLP-1 and calcitonin levels before and 2 weeks after bariatric surgery. MethodsPatients above 18 years of age who underwent either laparoscopic sleeve gastrectomy or Roux-en Y gastric bypass were recruited into the study. Measured indices were homeostatic model assessment 2 for insulin resistance (HOMA2-IR), an index for hepatic insulin resistance; Matsuda index, an index of whole body insulin sensitivity; and insulin secretion and sensitivity index (ISSI-2), a marker of beta cell secretion. ResultsTwenty eight patients completed the study. HOMA2-IR was lower (2.72 ± 1.28 vs. 2.04 ± 0.9; P = 0.001) and ISSI-2 was higher (0.80 (0.51–1.26) vs. 1.04 (0.56–1.38); P = 0.019) at 2 weeks after surgery compared to baseline. Matsuda index also improved after surgery but was not statistically significant (2.02 (1.1–2.94) vs. 2.84 (1.56–4.12); P = 0.078). Fasting GLP-1 and calcitonin levels did not change while both peak GLP-1, and area under curve for GLP-1 were higher after surgery. ConclusionsAt 2 weeks following bariatric surgery, hepatic insulin resistance decreased while beta cell function improved due to increase in postprandial GLP-1 level without any change in fasting calcitonin levels.

Roasting intensity of naturally low-caffeine Laurina coffee modulates glucose metabolism and redox balance in humans

ObjectiveCoffee consumption is negatively associated with risk of type 2 diabetes and cardiovascular mortality. Coffee roasting can greatly modify the quality-quantitative characteristics of bioactive compounds. We compared the effects of two different roasting intensities of the same naturally low-caffeine Arabica coffee variety (Laurina) on glucose and lipid metabolism as well as oxidative stress. MethodsWe performed a double-blind, crossover intervention study. Fourteen healthy male volunteers consumed four cups daily of light roasted coffee (LRC) and dark roasted coffee (DRC), each for 1 wk (intervention period 1 and 2 respectively). One wk washout, with total abstinence from coffee and other possible caffeine sources, preceded each intervention. Data were collected at the end of washout and intervention periods. ResultsChanges between washout and intervention periods in glucose concentrations at 2 h post–oral glucose tolerance test, were significantly lower after DRC than LRC intake (−0.6 ± 0.3 and 0.4 ± 0.3 mmol/L, P < 0.03). Changes in β-cell function, assessed as insulin secretion-sensitivity index-2, were significantly greater after DRC than LRC (34.7 ± 25.0 and −18.8 ± 21.0, P = 0.03). The initial (30 min) post–oral glucose tolerance test area under the curve of glucagon-like peptide-1 was 24± 9% greater (P = 0.03) after DRC than LRC. LRC or DRC did not affect insulin sensitivity. Changes from basal of reduced-to-oxidized glutathione ratio (GSH/GSSG) in erythrocytes were significantly greater after DRC than LRC (+1437 ± 371 and −152 ± 30, P < 0.05). The omega-3 index in erythrocyte membranes was 16± 4% greater (P < 0.001) after DRC than LRC. ConclusionsDRC consumption improved postload glucose metabolism by increasing incretin and insulin secretions. DRC compared to LRC improved redox balance and increased omega-3 fatty acids. Thus, we suggest greater metabolic benefits related to DRC.

Higher insulin and glucagon-like peptide-1 (GLP-1) levels in healthy, young South Asians as compared to Caucasians during an oral glucose tolerance test

ObjectiveHigher insulin levels during an oral glucose test (OGTT) have been shown in South Asians. We aimed to investigate if this increased insulin response causes reactive hypoglycemia later on, and if an increased glucagon-like-peptide-1 (GLP-1) response, which could contribute to the hyperinsulinemia, is present in this ethnic group. MethodsA prolonged, 6-h, 75-g OGTT was performed in healthy, young Caucasian (n=10) and South Asian (n=8) men. The glucose, insulin and GLP-1 response was measured and indices of insulin sensitivity and beta-cell activity were calculated. ResultsAge (Caucasians (CAU) 21.5±0.7years vs South Asians (SA) 21.4±0.7years (mean±SEM)) and body mass index (CAU 22.7±0.7kg/m2 vs SA 22.1±0.8kg/m2) were comparable between the two groups. South Asian men were more insulin resistant, as indicated by a comparable glucose but significantly higher insulin response, and a significantly lower Matsuda index (CAU 8.7(8.6) vs SA 3.2(19.2), median(IQR)). South Asians showed a higher GLP-1 response, as reflected by a higher area under the curve for GLP-1 (CAU 851±99.8mmol/l vs SA 1235±155.0mmol/L). During the whole 6-h period, no reactive hypoglycemia was observed. ConclusionHealthy, young South Asian men have higher insulin levels during an OGTT as compared to Caucasians. This does not, however, lead to reactive hypoglycemia. The hyperinsulinemia is accompanied by increased levels of GLP-1. Whether this is an adaptive response to facilitate hyperinsulinemia to overcome insulin resistance or reflects a GLP-1 resistant state has yet to be elucidated.