scholarly journals High DPP-4 Concentrations in Adolescents Are Associated With Low Intact GLP-1

2018 ◽  
Vol 103 (8) ◽  
pp. 2958-2966 ◽  
Author(s):  
Rasmus Stenlid ◽  
Hannes Manell ◽  
Maria Halldin ◽  
Joel Kullberg ◽  
Håkan Ahlström ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Plasma Concentrations ◽  
Tolerance Test ◽  
High Plasma ◽  
University Hospital ◽  
Liver Fat ◽  
Oral Glucose ◽  
Cross Sectional ◽  
Dipeptidyl Peptidase 4

Abstract Context Dipeptidyl peptidase 4 (DPP-4) metabolizes glucagon-like peptide-1 (GLP-1), and increased DPP4 levels are associated with obesity and visceral adiposity in adults. Objective Investigating DPP-4 levels in adolescents and their association with (1) circulating intact GLP-1 levels and glucose tolerance; (2) body mass index (BMI); and (3) visceral, subcutaneous, and liver fat compartments. Design Cross-sectional study, July 2012 to April 2015. Setting Pediatric obesity clinic, Uppsala University Hospital. Patients and Participants Children and adolescents with obesity (n = 59) and lean controls (n = 21) aged 8 to 18 years. Main Outcome Measures BMI SD score, fasting plasma concentrations of DPP-4, total and intact GLP-1, fasting and oral glucose tolerance test (OGTT) concentrations of glucose, and visceral adipose tissue (VAT) and subcutaneous adipose tissue volumes and liver fat fraction. Results Plasma DPP-4 levels decreased with age in both obese (41 ng/mL per year) and lean subjects (48 ng/mL per year). Plasma DPP-4 levels were higher in males in both the obesity and lean groups. With adjustments for age and sex, plasma DPP-4 level was negatively associated with intact GLP-1 at fasting (β = −12.3; 95% CI: −22.9, −1.8) and during OGTT (β = −12.1; 95% CI: −22.5, −1.7). No associations were found between DPP-4 and plasma glucose levels measured at fasting or after a 2-hour OGTT. Plasma DPP-4 level was 19% higher in obese subjects. Among adipose tissue compartments, the strongest association was with VAT (β = 0.05; 95% CI: −0.02, 0.12). Conclusions In adolescents, high plasma DPP-4 concentrations were associated with low proportions of intact GLP-1, high BMI, young age, and male sex. The observed associations are compatible with increased metabolism of GLP-1 in childhood obesity.

scholarly journals Altered Plasma Levels of Glucagon, GLP-1 and Glicentin During OGTT in Adolescents With Obesity and Type 2 Diabetes

2016 ◽  
Vol 101 (3) ◽  
pp. 1181-1189 ◽  
Author(s):  
Hannes Manell ◽  
Johan Staaf ◽  
Levon Manukyan ◽  
Hjalti Kristinsson ◽  
Jing Cen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Outcome Measures ◽  
Plasma Levels ◽  
Pediatric Obesity ◽  
Tolerance Test ◽  
University Hospital ◽  
Oral Glucose ◽  
Cross Sectional

Abstract Context: Proglucagon-derived hormones are important for glucose metabolism, but little is known about them in pediatric obesity and type 2 diabetes mellitus (T2DM). Objective: Fasting and postprandial levels of proglucagon-derived peptides glucagon, GLP-1, and glicentin in adolescents with obesity across the glucose tolerance spectrum were investigated. Design: This was a cross-sectional study with plasma hormone levels quantified at fasting and during an oral glucose tolerance test (OGTT). Setting: This study took place in a pediatric obesity clinic at Uppsala University Hospital, Sweden. Patients and Participants: Adolescents with obesity, age 10–18 years, with normal glucose tolerance (NGT, n = 23), impaired glucose tolerance (IGT, n = 19), or T2DM (n = 4) and age-matched lean adolescents (n = 19) were included. Main Outcome Measures: Outcome measures were fasting and OGTT plasma levels of insulin, glucagon, active GLP-1, and glicentin. Results: Adolescents with obesity and IGT had lower fasting GLP-1 and glicentin levels than those with NGT (0.25 vs 0.53 pM, P < .05; 18.2 vs 23.6 pM, P < .01) and adolescents with obesity and T2DM had higher fasting glucagon levels (18.1 vs 10.1 pM, P < .01) than those with NGT. During OGTT, glicentin/glucagon ratios were lower in adolescents with obesity and NGT than in lean adolescents (P < .01) and even lower in IGT (P < .05) and T2DM (P < .001). Conclusions: Obese adolescents with IGT have lowered fasting GLP-1 and glicentin levels. In T2DM, fasting glucagon levels are elevated, whereas GLP-1 and glicentin levels are maintained low. During OGTT, adolescents with obesity have more products of pancreatically than intestinally cleaved proglucagon (ie, more glucagon and less GLP-1) in the plasma. This shift becomes more pronounced when glucose tolerance deteriorates.

An open-label phase Ⅰ/Ⅱ a clinical trial of 11β-HSD1 inhibitor for Cushing’s syndrome and autonomous cortisol secretion

2021 ◽  
Author(s):  
Satoko Oda ◽  
Kenji Ashida ◽  
Makiko Uchiyama ◽  
Shohei Sakamoto ◽  
Nao Hasuzawa ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
University Hospital ◽  
Oral Glucose ◽  
Cortisol Secretion ◽  
Oral Glucose Tolerance ◽  
Open Label ◽  
Autonomous Cortisol Secretion

Abstract Context 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors demonstrate anti-metabolic and anti-sarcopenic effects in Cushing’s syndrome (CS) and autonomous cortisol secretion (ACS) patients. Objective To confirm the efficacy and safety of S-707106 (11β-HSD1 inhibitor) administered to CS and ACS patients. Design A 24-week single-center, open-label, single-arm, dose-escalation, investigator-initiated clinical trial on a database. Setting Kyushu University Hospital, Kurume University Hospital, and related facilities. Patients Sixteen patients with inoperable or recurrent CS and ACS, with mildly impaired glucose tolerance. Intervention Oral administration of 200-mg S-707106 after dinner, daily, for 24 weeks. In patients with insufficient improvement in oral glucose tolerance test results at 12 weeks, an escalated dose of S-707106 (200-mg BID) was administered for the residual 12 weeks. Main Outcome Measures The rate of participants responding to glucose tolerance impairment, defined as those showing a 25% reduction in the area under the curve (AUC) of plasma glucose during the 75 g-oral glucose tolerance test at 24 weeks. Results S-707106 administration could not achieve the primary endpoint of this clinical trial (>20% of responsive participants). AUC glucose decreased by -7.1% (SD, 14.8 [90% CI: -14.8– -1.0], P=0.033) and -2.7% (14.5 [-10.2–3.4], P=0.18) at 12 and 24 weeks, respectively. S-707106 administration decreased AUC glucose significantly in participants with a high body mass index. Body fat percentage decreased by -2.5% (1.7 [-3.3– -1.8], P<0.001), and body muscle percentage increased by 2.4% (1.6 [1.7–3.1], P<0.001). Conclusions S-707106 is an effective insulin sensitizer and anti-sarcopenic and anti-obesity medication for these patients.

scholarly journals Metabolic phenotype in Darier disease: a cross-sectional clinical study

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Tara Ahanian ◽  
Philip Curman ◽  
Ivone U. S. Leong ◽  
Kerstin Brismar ◽  
Etty Bachar-Wikstrom ◽  
...  
Keyword(s):  
Clinical Study ◽  
Glucose Tolerance ◽  
Er Stress ◽  
Glucose Tolerance Test ◽  
Fasting Blood Glucose ◽  
Tolerance Test ◽  
Metabolic Phenotype ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Cross Sectional

Abstract Background Human data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in diabetes is scarce. Darier disease (DD) is a hereditary skin disease caused by mutations in the ATP2A2 gene encoding the sarcoendoplasmic-reticulum ATPase 2 (SERCA2) calcium pump, which causes calcium dyshomeostasis and ER stress. We hypothesize that DD patients have a diabetes-like metabolic phenotype and the objective of this study was to examine the association between DD with impaired glucose tolerance and diabetes. Methods Cross-sectional clinical study on 25 DD patients and 25 matched controls. Metabolic status was assessed primarily by fasting blood glucose, oral glucose tolerance test, HOMA2-%S (insulin resistence) and HOMA2-%B (beta cell function). Results DD subjects showed normal oral glucose tolerance test and HOMA2-%S, while fasting blood glucose was lower and c-peptide as well as HOMA2-%B was higher. Conclusion Increased HOMA2-%B values are indicative of increased basal insulin secretion which is a type of beta cell dysfunction associated to diabetes development. These results supports a role of ER stress in diabetes pathophysiology and contribute to the understanding of DD as a multi-organ syndrome.

Diagnosis of cystic fibrosis-related glucose abnormalities: Can we shorten the standard oral glucose tolerance test?

2013 ◽  
Vol 38 (12) ◽  
pp. 1254-1259 ◽  
Author(s):  
Adèle Coriati ◽  
Belinda Elisha ◽  
Sandrine Virassamynaik ◽  
Maude Phaneuf ◽  
Sophie Ziai ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Diagnostic Value ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Cross Sectional ◽  
Diagnostic Values

Adult patients with cystic fibrosis (APCF) are at high risk of developing impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) and thus an annual screening with a 2-h oral glucose tolerance test (OGTT) is recommended. This population would greatly benefit from a simplified and harmless alternative to the standard OGTT. Thus, we aimed to compare the diagnostic values of HbA1c and glycemias at interval time points during the 2-h OGTT for IGT and CFRD detection in APCF. To do so, we conducted a cross-sectional analysis of 194 APCF with normal fasting plasma glucose values (≤7.0 mmol·L−1) who underwent a 2-h OGTT. Receivers operating characteristic area under the curves (ROC-AUC) were analyzed to assess the diagnostic value of HbA1c and intermediate OGTT glycemias using 2-h OGTT glycemia as reference. For both IGT and CFRD diagnoses, ROC-AUC values obtained from glycemia at 90 min were significantly higher than HbA1c and remaining intermediate glycemias (p < 0.001). The best 90-min OGTT cut-off values for these diagnoses were >9.3 mmol·L−1 (IGT) and ≥11.5 mmol·L−1 (CFRD). A 90-min OGTT glycemia might be a simplified alternative to 2-h OGTT glycemia for earlier glucose tolerance abnormalities diagnosis in APCF. This finding should be confirmed in other APCF cohorts and its predictive value should be established prospectively.

scholarly journals Hepatic fat and glucose tolerance in women with recent gestational diabetes

2018 ◽  
Vol 6 (1) ◽  
pp. e000549 ◽  
Author(s):  
Sadia Mehmood ◽  
Myles Margolis ◽  
Chang Ye ◽  
Louise Maple-Brown ◽  
Anthony J Hanley ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Post Partum ◽  
Tolerance Test ◽  
Liver Fat ◽  
Oral Glucose ◽  
Increased Risk ◽  
Hepatic Fat

ObjectiveWomen with a history of gestational diabetes mellitus (GDM) have an elevated risk of ultimately developing pre-diabetes and diabetes later in life. They also have an increased prevalence of fatty liver, but recent studies have reported conflicting findings on whether hepatic fat affects their risk of pre-diabetes/diabetes. Thus, we sought to evaluate the associations of liver fat with glucose homeostasis and determinants thereof in women with and without recent gestational dysglycemia.MethodsTwo hundred and fifty-seven women underwent an antepartum oral glucose tolerance test (OGTT), which diagnosed 97 with GDM, 40 with gestational impaired glucose tolerance (GIGT), and 120 with normal glucose tolerance (NGT). At a mean of 4.8 years post partum, they underwent an OGTT (which revealed that 52 had progressed to pre-diabetes/diabetes) and hepatic ultrasound, on which liver fat was graded as none (n=164), mild (n=66), or moderate (n=27).ResultsLiver fat was more prevalent in women with previous GDM than in those with GIGT or NGT (p=0.009) and in women with current pre-diabetes/diabetes than in those without (p=0.0003). As the severity of liver fat increased, there was a progressive worsening of insulin sensitivity and beta-cell function, coupled with rising fasting and 2-hour glucose (all p<0.0001). On multiple linear regression analyses, moderate liver fat was independently associated with lower insulin sensitivity (p=0.0002) and higher 2-hour glucose (p=0.009). Moreover, moderate liver fat emerged as an independent predictor of pre-diabetes/diabetes (OR=3.66, 95% CI 1.1 to 12.5).ConclusionThe higher prevalence of liver fat in women with previous GDM is associated with their increased risk of pre-diabetes/diabetes.

scholarly journals Effects of metformin on metabolism of white and brown adipose tissue in obese C57BL/6J mice

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Tao Yuan ◽  
Juan Li ◽  
Wei-Gang Zhao ◽  
Wei Sun ◽  
Shuai-Nan Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Brown Adipose Tissue ◽  
Tolerance Test ◽  
Normal Diet ◽  
The Body ◽  
Oral Glucose ◽  
Obese Mice ◽  
Brown Adipose

Abstract Background To investigate effects of metformin on the regulation of proteins of white adipose tissue (WAT) and brown adipose tissue (BAT) in obesity and explore the underlying mechanisms on energy metabolism. Methods C57BL/6J mice were fed with normal diet (ND, n = 6) or high-fat diet (HFD, n = 12) for 22 weeks. HFD-induced obese mice were treated with metformin (MET, n = 6). After treatment for 8 weeks, oral glucose tolerance test (OGTT) and hyperinsulinemic–euglycemic clamp were performed to evaluate the improvement of glucose tolerance and insulin sensitivity. Protein expressions of WAT and BAT in mice among ND, HFD, and MET group were identified and quantified with isobaric tag for relative and absolute quantification (iTRAQ) coupled with 2D LC–MS/MS. The results were analyzed by MASCOT, Scaffold and IPA. Results The glucose infusion rate in MET group was increased significantly compared with HFD group. We identified 4388 and 3486 proteins in WAT and BAT, respectively. As compared MET to HFD, differential expressed proteins in WAT and BAT were mainly assigned to the pathways of EIF2 signaling and mitochondrial dysfunction, respectively. In the pathways, CPT1a in WAT, CPT1b and CPT2 in BAT were down-regulated by metformin significantly. Conclusions Metformin improved the body weight and insulin sensitivity of obese mice. Meanwhile, metformin might ameliorate endoplasmic reticulum stress in WAT, and affect fatty acid metabolism in WAT and BAT. CPT1 might be a potential target of metformin in WAT and BAT.

scholarly journals Inflammatory mediators in morbidly obese subjects: associations with glucose abnormalities and changes after oral glucose

2009 ◽  
Vol 161 (3) ◽  
pp. 451-458 ◽  
Author(s):  
Dag Hofsø ◽  
Thor Ueland ◽  
Helle Hager ◽  
Trond Jenssen ◽  
Jens Bollerslev ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Inflammatory Mediators ◽  
Interleukin 1 ◽  
Tolerance Test ◽  
Normal Glucose Tolerance ◽  
Normal Weight ◽  
Morbidly Obese ◽  
Oral Glucose ◽  
Cross Sectional ◽  
Normal Glucose

ObjectiveTo explore inflammatory mediators in morbidly obese (MO) subjects with various categories of glucose tolerance and to study the changes in these mediators after an oral glucose load.DesignCross-sectional and experimental study.MethodsA total of 144 MO subjects were classified into three categories: normal glucose tolerance (NGT); pre-diabetes; and new onset diabetes mellitus (NODM) were included, as were 27 normal weight normoglycemic controls. Serum osteoprotegerin (OPG), visfatin, leptin, adiponectin, interleukin-1 receptor antagonist (IL-1Ra), and C-reactive protein (CRP) were analyzed during an oral glucose tolerance test (OGTT).ResultsFasting levels of leptin and IL-1Ra were consistently higher in obese persons (P<0.001 and P<0.05). MO subjects with NGT had higher CRP levels (P<0.001) and lower adiponectin levels (P<0.05) compared to controls. Yet when compared with MO subjects with NODM, those with NGT had lower CRP levels and higher adiponectin levels (both P<0.05). Baseline OPG and visfatin levels did not differ between the groups (P=0.326 and P=0.198). During OGTT, OPG levels decreased (P<0.001) and visfatin levels increased transiently (P=0.018). The response in OPG and visfatin did not differ between the groups (P=0.690 and P=0.170). There were minor changes in adiponectin and leptin levels.ConclusionsMorbid obesity and glucose intolerance were associated with lower adiponectin levels and higher CRP levels, thus supporting a relationship between obesity, glucose homeostasis, and inflammation. Oral glucose suppressed OPG levels and transiently enhanced visfatin levels independent of obesity and glucose tolerance status, indicating that glucose may be involved in the acute regulation of these proteins.

scholarly journals Simultaneous analyses of carbohydrate-mediated serum GLP-1 and GLP-2 and duodenal receptor expression in children with and without celiac disease

2019 ◽  
Vol 12 ◽  
pp. 175628481984275 ◽  
Author(s):  
Marianna Rachmiel ◽  
Gilad Ben-Yehudah ◽  
Haim Shirin ◽  
Efrat Broide
Keyword(s):  
Celiac Disease ◽  
Plasma Concentrations ◽  
Serum Levels ◽  
Tolerance Test ◽  
Receptor Expression ◽  
Control Group ◽  
Oral Glucose ◽  
Positive Serology ◽  
Cross Sectional ◽  
Group Assignment

Background: Variability in glucagon-like peptide (GLP)-1 and GLP-2 plasma concentrations has been suggested in Celiac disease (CD), with inconclusive results. We assessed the association between serum levels of GLP-1 and GLP-2 and their duodenal receptor expression in children with and without CD. Methods: This was a two-part, cross-sectional and prospective cohort study. Group assignment, performed after duodenal samples for mRNA expression of GLP-1 receptor (GLP1R) and GLP-2 receptor (GLP2R), were taken during esophagogastroduodenoscopy. The control group consisted of patients with normal endoscopy and negative serology. The CD group consisted of patients with positive serology and endoscopy suggestive of CD. All had an oral glucose-tolerance test (OGTT). CD patients underwent a second OGTT after 6 months of a gluten-free diet (GFD). Results: The CD group included 12 patients; 7 males with mean age 9.2 ± 2.5 years. The control group included 10 patients; 5 males with mean age 12 ± 4 years, ( p = 0.14). No differences were detected in basal or peak levels of GLP-1 or GLP-2 between control, naïve CD (before GFD) and treated CD (after GFD) groups. Expression of GLP1R and GLP2R mRNA was similar. Significant positive correlations between glucose and C-peptide secretion ( r = 0.9, p < 0.01) and GLP-1 and GLP-2 ( r = 0.8, p = 0.01) were detected in the control group. Significant negative correlations were found in the naïve CD group between GLP2R expression and glucose secretion ( r = −0.68, p = 0.015) and GLP1R expression and serum GLP-1 ( r = −0.7, p = 0.016). Conclusions: Although no significant differences were detected in secretion patterns or gut receptor expression of GLP-1 and GLP-2 in healthy versus CD pediatric patients, the detected discrepancy between the ligand levels and their tissue receptors requires additional study.

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