Acute and 2-week exposure to prednisolone impair different aspects of β-cell function in healthy men

ObjectiveGlucocorticoids (GCs), such as prednisolone, are associated with adverse metabolic effects, including glucose intolerance and diabetes. In contrast to the well known GC-induced insulin resistance, the effects of GCs on β-cell function are less well established. We assessed the acute and short-term effects of prednisolone treatment on β-cell function in healthy men.Research design and methodsA randomised, double-blind, placebo-controlled trial consisting of two protocols was conducted. In protocol 1 (n=6), placebo and a single dose of 75 mg of prednisolone were administered. In protocol 2 (n=23), participants received 30 mg of prednisolone daily or placebo for 15 days. Both empirical and model-based parameters of β-cell function were calculated from glucose, insulin and C-peptide concentrations obtained during standardised meal tests before and during prednisolone treatment (protocols 1 and 2), and 1 day after cessation of treatment (protocol 2).ResultsSeventy-five milligrams of prednisolone acutely increased the area under the postprandial glucose curve (AUCgluc;P=0.005), and inhibited several parameters of β-cell function, including AUCc-pep/AUCglucratio (P=0.004), insulinogenic index (P=0.007), glucose sensitivity (P=0.02) and potentiation factor ratio (PFR;P=0.04). A 15-day treatment with prednisolone increased AUCgluc(P<0.001), despite augmented C-peptide secretion (P=0.05). β-cell function parameters were impaired, including the fasting insulin secretory tone (P=0.02) and PFR (P=0.007).ConclusionsAcute and short-term exposure to prednisolone impairs different aspects of β-cell function, which contribute to its diabetogenic effects.

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FRI0322 INSULIN RESISTANCE IN NON-DIABETES PATIENTS WITH SPONDYLOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.619 ◽

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.

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Beneficial Effects of Insulin on Glycemic Control and β-Cell Function in Newly Diagnosed Type 2 Diabetes With Severe Hyperglycemia After Short-Term Intensive Insulin Therapy

Yearbook of Endocrinology ◽

10.1016/s0084-3741(09)79407-7 ◽

2009 ◽

Vol 2009 ◽

pp. 41-42

Author(s):

F. Ovalle

Keyword(s):

Type 2 Diabetes ◽

Glycemic Control ◽

Intensive Insulin Therapy ◽

Cell Function ◽

Newly Diagnosed ◽

Β Cell ◽

Short Term ◽

Beneficial Effects ◽

Β Cell Function

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab692 ◽

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<0.001) and oDIcpeptide (C-peptide index)(1/cpep0) (r=-0.48, p<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.

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

BMC Pediatrics ◽

10.1186/s12887-020-02339-8 ◽

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.

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Circulating Spexin Decreased and Negatively Correlated with Systemic Insulin Sensitivity and Pancreatic β Cell Function in Obese Children

Annals of Nutrition and Metabolism ◽

10.1159/000496459 ◽

2019 ◽

Vol 74 (2) ◽

pp. 125-131 ◽

Cited By ~ 7

Author(s):

Ting Chen ◽

Fengyun Wang ◽

Zhenyu Chu ◽

Ling Sun ◽

Haitao Lv ◽

...

Keyword(s):

Blood Pressure ◽

Insulin Sensitivity ◽

Cell Function ◽

Insulinogenic Index ◽

Model Assessment ◽

Pancreatic Β Cell ◽

Obese Children ◽

Β Cell ◽

Β Cell Function ◽

Obese Subjects

Objectives: Spexin (SPX) is a novel peptide that has recently emerged as an important regulatory adipokine of obesity and related metabolic disease. Little is known about its role in children. The aim of the current study was to determine the potential role of SPX in obese children and explore its relationships with obesity-related markers, insulin sensitivity and pancreatic β cell function. Method: We studied the levels of serum SPX in 40 obese and 32 normal weight pre-puberty children (mean age was 8.59 ± 1.82 and 8.15 ± 2.03 years in obesity and control groups respectively). We investigated the levels of body mass index, blood pressure, lipids, glucose, insulin, Homeostasis model assessment for insulin-resistant (HOMA-IR, HOMA for β-cell function [HOMA-β]), insulinogenic index and C-peptide index and analyzed their correlations with SPX levels. Results: SPX levels were significantly decreased in obese children compared to controls. Moreover, serum SPX levels were lower in IR obese subjects in contrast with the non-IR obese subjects. Serum SPX concentrations correlated negatively and significantly with triglycerides, systolic blood pressure, diastolic blood pressure, fasting insulin level, HOMA-IR, insulinogenic index, and HOMA-β levels in obese children. Conclusions: In summary, serum SPX levels significantly decreased in obese children and negatively correlated with insulin resistance and pancreatic β cell function indicators. Therefore, SPX may play a protective role in the process of glucose homeostasis and is closely related to β cell function in obese children.

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Two-year trial of intermittent insulin therapy vs metformin for the preservation of β-cell function after initial short-term intensive insulin induction in early type 2 diabetes

Diabetes Obesity and Metabolism ◽

10.1111/dom.13236 ◽

2018 ◽

Vol 20 (6) ◽

pp. 1399-1407 ◽

Cited By ~ 12

Author(s):

Ravi Retnakaran ◽

Haysook Choi ◽

Chang Ye ◽

Caroline K. Kramer ◽

Bernard Zinman

Keyword(s):

Type 2 Diabetes ◽

Insulin Therapy ◽

Cell Function ◽

Early Type ◽

Β Cell ◽

Short Term ◽

Β Cell Function

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

Acta Endocrinologica ◽

10.1530/eje-10-0282 ◽

2010 ◽

Vol 163 (2) ◽

pp. 225-231 ◽

Cited By ~ 10

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.

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