scholarly journals FRI0322 INSULIN RESISTANCE IN NON-DIABETES PATIENTS WITH SPONDYLOARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 752.2-753
Author(s):  
J. C. Quevedo-Abeledo ◽  
F. Genre ◽  
J. Rueda-Gotor ◽  
A. Corrales ◽  
V. Hernández-Hernández ◽  
...  
Keyword(s):  
Cell Function ◽  
Inflammatory Diseases ◽  
Univariate Analysis ◽  
Serum Levels ◽  
Β Cell ◽  
Related Factors ◽  
C Peptide ◽  
Related Data ◽  
Β Cell Function ◽  
Beta Coefficient

Background:Insulin resistance (IR) is a state in which a given concentration of insulin is associated with a subnormal glucose response. IR constitutes a major underlying abnormality driving cardiovascular disease in the general population and has been linked to inflammatory diseases. In this sense, several reports have confirmed that inflammation worsens IR and impairs pancreatic β-cell function in inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus.Objectives:In this study we aimed to determine the prevalence of IR in patients with spondyloarthritis (SpA) compared to controls, and whether IR can be explained by disease-related features in SpA patients.Methods:Study of 577 subjects, 306 patients diagnosed with SpA according to ASAS criteria and 271 controls. Insulin and C-peptide serum levels, IR and β-cell function (%B) indexes by homeostatic model assessment (HOMA2), and lipid profiles were assessed in patients and controls. A multivariate regression analysis was performed to evaluate the differences in IR indexes between patients and controls and to determine how IR is associated with disease-related characteristics.Results:SpA patients showed higher serum levels of insulin (8.7 [4.8-15.9] vs. 8.0 [5.7-11.2] uU/ml, p=0.001) and C peptide (1.4 [0.7-2.5] vs. 1.2 [0.7-1.7] ng/ml, p=0.000) than controls in the univariate analysis. Similarly, HOMA2-B% and IR were all significantly higher in SpA patients. These differences were still evident when the comparisons were made after the multivariate analysis had been adjusted for traditional IR-related factors (sex, age, BMI, hypertension, dyslipidemia, smoking and, cholesterol), glucocorticoids intake, insulin and C-peptide. Moreover, HOMA2-B% and HOMA2-IR scores, both calculated with insulin or C-peptide, yielded statistically higher significant values in SpA patients than controls.Classic IR-related factors (age, BMI, waist circumference, hypertension, obesity, dyslipidemia, atherogenic index, and triglycerides), as well as CRP serum levels, were all related, to a greater or lesser degree, with IR and β-cell function. Regarding disease-related data, ASDAS-CRP, BASFI and BASMI scores were positively associated with IR; and BASMI and BASDAI scores were positively related to HOMA2-%B-C peptide. Moreover, the use of NSAID and prednisone were, respectively, positive and negatively related to β-cell function. However, only some of the associations of the univariate analysis were maintained after adjusting for confounders. In this sense, disease duration (beta coefficient 2 [95% CI 1-3], p=0.001) and positivity for HLA-B27 (beta coefficient 30 [95% CI 12-49], p=0.002) were associated with higher β-cell functionality after the multivariate analysis.Conclusion:Patients with SpA have an increased IR compared to controls. SpA disease-related data like disease duration and HLA-B27 are independently associated with β-cell dysfunction.Disclosure of Interests:Juan Carlos Quevedo-Abeledo Speakers bureau: Abbvie, Fernanda Genre: None declared, Javier Rueda-Gotor: None declared, Alfonso Corrales Speakers bureau: Abbvie, Vanessa Hernández-Hernández Speakers bureau: Pfizer, Abbvie, MSD, Natalia Fañanas-Rodríguez: None declared, Bernardo Lavín-Gómez: None declared, delgado frias esmeralda Speakers bureau: Pfizer, Abbvie, MSD, Antonia de Vera-González: None declared, Alejandra Delgado-González: None declared, Laura de Armas-Rillo: None declared, Maria Teresa García-Unzueta: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Iván Ferraz-Amaro Grant/research support from: Pfizer, Abbvie, Speakers bureau: Pfizer, Abbvie, MSD.

Let7b-5p is Upregulated in the Serum of Emirati Patients with Type 2 Diabetes and Regulates Insulin Secretion in INS-1 Cells

2020 ◽  
Author(s):  
Hayat Aljaibeji ◽  
Noha Mousaad Elemam ◽  
Abdul Khader Mohammed ◽  
Hind Hasswan ◽  
Mahammad Al Thahyabat ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Viability ◽  
Cell Function ◽  
Serum Levels ◽  
Insulin Content ◽  
Β Cell ◽  
Control Subjects ◽  
Β Cell Function

Abstract Let7b-5p is a member of the Let-7 miRNA family and one of the top expressed miRNAs in human islets that implicated in glucose homeostasis. The levels of Let7b-5p in type 2 diabetes (T2DM) patients or its role in β-cell function is still unclear. In the current study, we measured the serum levels of let7b-5p in Emirati patients with T2DM (with/without complications) and control subjects. Overexpression or silencing of let7b-5p in INS-1 (832/13) cells was performed to investigate the impact on insulin secretion, content, cell viability, apoptosis, and key functional genes. We found that serum levels of let7b-5p are significantly (p<0.05) higher in T2DM-patients or T2DM with complications compared to control subjects. Overexpression of let7b-5p increased insulin content and decreased glucose-stimulated insulin secretion, whereas silencing of let7b-5p reduced insulin content and secretion. Modulation of the expression levels of let7b-5p did not influence cell viability nor apoptosis. Analysis of mRNA and protein expression of hallmark genes in let7b-5p transfected cells revealed a marked dysregulation of Insulin, Pancreatic And Duodenal Homeobox 1 (PDX1), glucokinase (GCK), glucose transporter 2 (GLUT2), and INSR. In conclusion, an appropriate level of let7b-5p is essential to maintain β-cell function and may be regarded as a biomarker for T2DM.

Full The Relationship between Continuous Glucose Monitoring and OGTT in Youth and Young Adults with Cystic Fibrosis

2021 ◽  
Author(s):  
Christine L Chan ◽  
Laura Pyle ◽  
Tim Vigers ◽  
Philip S Zeitler ◽  
Kristen J Nadeau
Keyword(s):  
Cystic Fibrosis ◽  
Continuous Glucose Monitoring ◽  
Cell Function ◽  
Glucose Monitoring ◽  
Oral Glucose ◽  
Β Cell ◽  
Oral Glucose Tolerance Testing ◽  
C Peptide ◽  
Β Cell Function ◽  
The Relationship

Abstract Context Early glucose abnormalities in people with CF (PwCF) are commonly detected by continuous glucose monitoring (CGM). Relationships between these CGM abnormalities and oral glucose tolerance testing (OGTT) in PwCF have not been fully characterized. Objective(s) 1) To determine the relationship between CGM and common OGTT-derived estimates of β-cell function, including C-peptide index and oral disposition index (oDI) and 2) to explore whether CGM can be used to screen for OGTT-defined prediabetes and cystic fibrosis related diabetes (CFRD). Study Design/Methods PwCF not on insulin and healthy controls ages 6-25 yrs were enrolled in a prospective study collecting OGTT and CGM. A subset underwent frequently-sampled OGTTs (fsOGTT) with 7-point glucose, insulin, and C-peptide measurements. Pearson’s correlation coefficient was used to test the association between select CGM and fsOGTT measures. ROC analysis was applied to CGM variables to determine the cutoff optimizing sensitivity and specificity for detecting prediabetes and CFRD. Results A total of 120 participants (controls=35, CF=85), including 69 with fsOGTTs, were included. CGM coefficient of variation correlated inversely with C-peptide index (Cpeptide30-Cpeptide0/Glucose30-Glucose0) (r=-0.45, p&lt;0.001) and oDIcpeptide (C-peptide index)(1/cpep0) (r=-0.48, p&lt;0.0001). In PwCF, CGM variables had ROC-AUCs ranging from 0.43-0.57 for prediabetes and 0.47-0.6 for CFRD. Conclusions Greater glycemic variability on CGM correlated with reduced β-cell function. However, CGM performed poorly at discriminating individuals with and without OGTT-defined CFRD and prediabetes. Prospective studies are now needed to determine how well the different tests predict clinically-relevant non-glycemic outcomes in PwCF.

scholarly journals Systemic TNFα correlates with residual β-cell function in children and adolescents newly diagnosed with type 1 diabetes

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Anne Julie Overgaard ◽  
Jens Otto Broby Madsen ◽  
Flemming Pociot ◽  
Jesper Johannesen ◽  
Joachim Størling
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Disease Onset ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Entire Study ◽  
C Peptide ◽  
Disease Remission ◽  
Β Cell Function

Abstract Background Type 1 diabetes (T1D) is caused by immune-mediated destruction of the β-cells. After initiation of insulin therapy many patients experience a period of improved residual β-cell function leading to partial disease remission. Cytokines are important immune-modulatory molecules and contribute to β-cell damage in T1D. The patterns of systemic circulating cytokines during T1D remission are not clear but may constitute biomarkers of disease status and progression. In this study, we investigated if the plasma levels of various pro- and anti-inflammatory cytokines around time of diagnosis were predictors of remission and residual β-cell function in children with T1D followed for one year after disease onset. Methods In a cohort of 63 newly diagnosed children (33% females) with T1D with a mean age of 11.3 years (3.3–17.7), ten cytokines were measured of which eight were detectable in plasma samples by Mesoscale Discovery multiplex technology at study start and after 6 and 12 months. Linear regression models were used to evaluate association of cytokines with stimulated C-peptide. Results Systemic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-6 inversely correlated with stimulated C-peptide levels over the entire study (P < 0.05). The concentrations of TNFα and IL-10 at study start predicted stimulated C-peptide level at 6 months (P = 0.011 and P = 0.043, respectively, adjusted for sex, age, HbA1c and stage of puberty). Conclusions In recent-onset T1D, systemic cytokine levels, and in particular that of TNFα, correlate with residual β-cell function and may serve as prognostic biomarkers of disease remission and progression to optimize treatment strategies. Trial Registration The study was performed according to the criteria of the Helsinki II Declaration and was approved by the Danish Capital Region Ethics Committee on Biomedical Research Ethics (journal number H-3-2014-052). The parents of all participants gave written consent.

scholarly journals The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study

Endocrine ◽  
2020 ◽  
Author(s):  
Sandro La Vignera ◽  
Rossella Cannarella ◽  
Fabio Galvano ◽  
Agata Grillo ◽  
Antonio Aversa ◽  
...  
Keyword(s):  
Body Weight ◽  
Ketogenic Diet ◽  
Cell Function ◽  
Serum Levels ◽  
Overweight And Obesity ◽  
Total Testosterone ◽  
Homa Index ◽  
Β Cell ◽  
Anthropometric Parameters ◽  
C Peptide

Abstract Background Overweight and obesity are increasingly spread in our society. Low testosterone levels are often present in these patients, the so-called metabolic hypogonadism, that further alters the metabolic balance in a sort of vicious cycle. Very low-calorie ketogenic diet (VLCKD) has been reported to efficiently reduce body weight, glycaemia, and the serum levels of insulin, glycated hemoglobin, but its effects on β-cell function and total testosterone (TT) levels are less clear. Aim To evaluate the effects of VLCKD on markers suggested to be predictive of β-cell dysfunction development, such as proinsulin or proinsulin/insulin ratio, and on TT values in a cohort of overweight or obese nondiabetic male patients with metabolic hypogonadism. Methods Patients with overweight or obesity and metabolic hypogonadism underwent to VLCKD for 12 weeks. Anthropometric parameters, blood testing for the measurement of glycaemia, insulin, C-peptide, proinsulin, TT, calculation of body-mass index (BMI), and HOMA index were performed before VLCKD and after 12 weeks. Results Twenty patients (mean age 49.3 ± 5.2 years) were enrolled. At enrollement all patients presented increased insulin, HOMA index, C-peptide, and proinsulin levels, whereas the proinsulin/insulin ratio was within the normal values. After VLCKD treatment, body weight and BMI significantly decreased, and 14.9 ± 3.9% loss of the initial body weight was achieved. Glycaemia, insulin, HOMA index, C-peptide, and proinsulin significantly decreased compared to pre-VLCKD levels. Serum glycaemia, insulin, C-peptide, and proinsulin levels returned within the normal range in all patients. No difference in the proinsulin/insulin ratio was observed after VLCKD treatment. A mean increase of 218.1 ± 53.9% in serum TT levels was achieved and none of the patients showed TT values falling in the hypogonadal range at the end of the VLCKD treatment. Conclusions This is the first study that evaluated the effects of VLCKD on proinsulin, proinsulin/insulin ratio, and TT levels. VLCKD could be safely used to improve β-cell secretory function and insulin-sensitivity, and to rescue overweight and obese patients from β-cell failure and metabolic hypogonadism.

scholarly journals Acute effects of hydrocortisone on the metabolic response to a glucose load: increase in the first-phase insulin secretion

2010 ◽  
Vol 163 (2) ◽  
pp. 225-231 ◽  
Author(s):  
Greisa Vila ◽  
Michael Krebs ◽  
Michaela Riedl ◽  
Sabina M Baumgartner-Parzer ◽  
Martin Clodi ◽  
...  
Keyword(s):  
Science Studies ◽  
Cell Function ◽  
Metabolic Response ◽  
Peptide Yy ◽  
Β Cell ◽  
C Peptide ◽  
Glucose Levels ◽  
Load Increase ◽  
Β Cell Function ◽  
First Phase Insulin Secretion

Background and aimSeveral basic science studies support the existence of non-genomic glucocorticoid signaling in pancreas, liver, and adipocytes, but its clinical relevance has not yet been elucidated. This study aimed at investigating the rapid effects of hydrocortisone on the human metabolic response to glucose.Subjects and methodsIn a randomized placebo-controlled crossover study, ten healthy men received an i.v. bolus of 0.6 mg/kg hydrocortisone once and placebo once 4 min before the administration of 330 mg/kg glucose. Cortisol, glucose, insulin, C-peptide, ghrelin, and peptide YY (PYY) levels were measured during the following 3 h. Minimal model analysis was performed for evaluating the metabolic response.ResultsHydrocortisone attenuated the rise in plasma glucose during the initial 15 min following glucose administration (P=0.039), and it led to lower glucose levels during the first 2 h (P=0.017). This was accompanied by enhanced circulating insulin (P=0.02) and C-peptide (P=0.03) levels during the initial 15 min, and a 35% increase in the first-phase β-cell function (P=0.003). Hydrocortisone decreased PYY concentrations during the initial 30 min (P=0.014), but it did not affect the ghrelin response to glucose.ConclusionOne i.v. bolus of hydrocortisone induces rapid effects on carbohydrate metabolism increasing the first-phase β-cell function. The modulation of PYY plasma levels suggests the possible non-genomic effects of glucocorticoids on appetite-regulatory hormones.

scholarly journals Frequent Monitoring of C-Peptide Levels in Newly Diagnosed Type 1 Subjects Using Dried Blood Spots Collected at Home

2018 ◽  
Vol 103 (9) ◽  
pp. 3350-3358 ◽  
Author(s):  
Ruben H Willemsen ◽  
Keith Burling ◽  
Peter Barker ◽  
Fran Ackland ◽  
Renuka P Dias ◽  
...  
Keyword(s):  
Cell Function ◽  
Dried Blood Spots ◽  
Diabetes Duration ◽  
Β Cell ◽  
C Peptide ◽  
Blood Spots ◽  
Β Cell Function ◽  
Over Time ◽  
At Home

Abstract Objective To evaluate an approach to measure β-cell function by frequent testing of C-peptide concentrations in dried blood spots (DBSs). Patients Thirty-two children, aged 7 to 17 years, with a recent diagnosis of type 1 diabetes. Design Mixed-meal tolerance test (MMTT) within 6 and again at 12 months after diagnosis, with paired venous and DBS C-peptide sampling at 0 and 90 minutes. Weekly DBS C-peptide before and after standardized breakfasts collected at home. Results DBS and plasma C-peptide levels (n = 115) correlated strongly (r = 0·91; P &lt; 0.001). The Bland-Altman plot indicated good agreement. The median number of home-collected DBS cards per participant was 24 over a median of 6.9 months. Repeated DBS C-peptide levels varied considerably within and between subjects. Adjustment for corresponding home glucose measurements reduced the variance, permitting accurate description of changes over time. The correlation of the C-peptide slope over time (assessed by repeated home DBS) vs area under the curve during the two MMTTs was r = 0.73 (P &lt; 0.001). Mixed models showed that a 1-month increase in diabetes duration was associated with 17-pmol/L decline in fasting DBS C-peptide, whereas increases of 1 mmol/L in glucose, 1 year older age at diagnosis, and 100 pmol/L higher baseline plasma C-peptide were associated with 18, 17, and 61 pmol/L higher fasting DBS C-peptide levels, respectively. In addition, glucose responsiveness decreased with longer diabetes duration. Conclusion Our approach permitted frequent assessment of C-peptide, making it feasible to monitor β-cell function at home. Evaluation of changes in the slope of C-peptide through this method may permit short-term evaluation of promising interventions.

scholarly journals Ectopic Fat Storage in the Pancreas, Liver, and Abdominal Fat Depots: Impact on β-Cell Function in Individuals with Impaired Glucose Metabolism

2011 ◽  
Vol 96 (2) ◽  
pp. 459-467 ◽  
Author(s):  
N. J. van der Zijl ◽  
G. H. Goossens ◽  
C. C. M. Moors ◽  
D. H. van Raalte ◽  
M. H. A. Muskiet ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Magnetic Resonance ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Ectopic Fat ◽  
Β Cell ◽  
C Peptide ◽  
Pancreatic Fat ◽  
Β Cell Function ◽  
Peptide Secretion

abstract Context: Pancreatic fat content (PFC) may have deleterious effects on β-cell function. Objective: We hypothesized that ectopic fat deposition, in particular pancreatic fat accumulation, is related to β-cell dysfunction in individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Design, Setting and Participants: This was a cross-sectional study in 64 age- and body mass index-matched individuals, with normal glucose tolerance (NGT; n = 16, 60% males), IFG (n = 29, 52% males), or IFG/IGT (n = 19, 63% males) was conducted. Intervention and Main Outcome Measures: Participants underwent the following: 1) a combined hyperinsulinemic-euglycemic and hyperglycemic clamp, with subsequent arginine stimulation to quantify insulin sensitivity and β-cell function; 2) proton-magnetic resonance spectroscopy to assess PFC and liver fat content (LFC); and 3) magnetic resonance imaging to quantify visceral (VAT) and sc (SAT) adipose tissue. The disposition index (DI; insulin sensitivity adjusted β-cell function) was assessed. Results: IFG and IFG/IGT were more insulin resistant (P &lt; 0.001) compared with NGT. Individuals with IFG/IGT had the lowest values of glucose- and arginine-stimulated C-peptide secretion (both P &lt; 0.03) and DI (P &lt; 0.001), relative to IFG and NGT. PFC and LFC gradually increased between NGT, IFG, and IFG/IGT (P = 0.02 and P = 0.01, respectively), whereas VAT and SAT were similar between groups. No direct associations were found between PFC, LFC, VAT, and SAT and C-peptide secretion. The DI was inversely correlated with PFC, LFC, and VAT (all P &lt; 0.05). Conclusions: PFC was increased in individuals with IFG and/or IGT, without a direct relation with β-cell function.

Pancreatic β-cell function in cirrhotic patients with and without overt diabetes. C-peptide response to glucagon and to meal

Metabolism ◽  
1985 ◽  
Vol 34 (8) ◽  
pp. 695-701 ◽  
Author(s):  
G. Marchesini ◽  
A. Melli ◽  
G.A. Checchia ◽  
Loretta Mattioli ◽  
M. Capelli ◽  
...  
Keyword(s):  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
C Peptide ◽  
Overt Diabetes ◽  
Β Cell Function ◽  
Cirrhotic Patients

scholarly journals The Influence of the Levonorgestrel-Releassing Intrauterine System (Lng Ius) on Metabolic Markers in Women with Normal Body Mass and Overweight Women

2013 ◽  
Vol 13 (2) ◽  
pp. 27-32
Author(s):  
Ineta Vasaraudze ◽  
Dace Rezeberga ◽  
Renars Erts ◽  
Aivars Lejnieks
Keyword(s):  
Insulin Sensitivity ◽  
Body Mass ◽  
Cell Function ◽  
Fasting Glucose ◽  
Density Lipoprotein ◽  
Β Cell ◽  
C Peptide ◽  
Overweight Women ◽  
Normal Body ◽  
Β Cell Function

Abstract Introduction. In Latvia, the number of overweight women is increasing, while the rate of cardio vascular disease (CVD) is one of the highest in the European Union. The influence of hormonal contraception on the development of CVD has not been studied in Latvia so far. Aim of the study. A nonrandomized open-label prospective trial of healthy reproductive-age women desiring to use the LNG IUS. Materials and methods. Before starting the use of contraception and six months after starting the use of contraception, the homeostasis model assessment insulin resistant (HOMA-IR) score, insulin sensitivity (HOMA-%S) and β-cell function (HOMA-%B) were calculated using fasting glucose (FG) and C peptide values. There were also determined other cardio-metabolic parameters: total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride level, systolic and diastolic blood pressure, and abdominal circumference. Results. Thirty women were involved in the study: seventeen women with a normal body-mass index (BMI) (BMI below 25) and thirteen overweight women (BMI above 25). When using the LNG IUS, the fasting glucose level increased in women with normal body mass, the level of insulin sensitivity decreased in both study groups; C peptide level, β-cell function and insulin resistance increased in both groups, but the changes were not statistically reliable (p>0.05). Conclusion. Although during the study there were determined changes in the FG level, insulin sensitivity, C peptide, β-cell function and insulin resistance parameters, these changes are not clinically significant, and the LNG IUS may be safely used clinically both by women with normal body mass and overweight women.

scholarly journals Genetic Composition and Autoantibody Titers Model the Probability of Detecting C-Peptide Following Type 1 Diabetes Diagnosis

2021 ◽  
Author(s):  
MacKenzie D. Williams ◽  
Rhonda Bacher ◽  
Daniel J. Perry ◽  
C. Ramsey Grace ◽  
Kieran M. McGrail ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Duration ◽  
Cell Function ◽  
Age At Onset ◽  
Diabetes Diagnosis ◽  
Β Cell ◽  
C Peptide ◽  
Peptide Detection ◽  
Β Cell Function

We and others previously demonstrated that a type 1 diabetes genetic risk score (GRS) improves the ability to predict disease progression and onset in at-risk subjects with islet autoantibodies. Here, we hypothesized that GRS and islet autoantibodies, combined with age at onset and disease duration, could serve as markers of residual β-cell function following type 1 diabetes diagnosis. Generalized estimating equations were used to investigate whether GRS along with insulinoma-associated protein-2 autoantibody (IA-2A), zinc transporter 8 autoantibody (ZnT8A) and GAD autoantibody (GADA) titers were predictive of C-peptide detection in a largely cross-sectional cohort of 401 subjects with type 1 diabetes (duration median = 4.5 years, range 0-60). Indeed, a combined model incorporating disease duration, age at onset, GRS, and titers of IA-2A, ZnT8A and GADA provided superior capacity to predict C-peptide detection (QIC=334.6) compared with disease duration, age at onset, and GRS as the sole parameters (QIC=359.2). These findings support the need for longitudinal validation of our combinatorial model. The ability to project the rate and extent of decline in residual C-peptide production for individuals with type 1 diabetes could critically inform enrollment and benchmarking for clinical trials seeking to preserve or restore endogenous β-cell function.

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