Relationship Between Insulin Sensitivity and β-Cell Secretion in Nondiabetic Subjects with Rheumatoid Arthritis

2018 ◽  
Vol 46 (3) ◽  
pp. 229-236 ◽  
Author(s):  
Beatriz Tejera-Segura ◽  
Raquel López-Mejías ◽  
Antonia M. de Vera-González ◽  
Alejandro Jiménez-Sosa ◽  
José M. Olmos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Multivariable Analysis ◽  
Molar Ratio ◽  
Hyperbolic Function ◽  
Healthy Individuals ◽  
Related Factors ◽  
Hyperbolic Relation ◽  
Hyperbolic Equilibrium

Objective.In nondiabetic healthy individuals, insulin secretion and sensitivity are linked by a negative feedback loop characterized by a hyperbolic function. We aimed to study the association of traditional insulin resistance (IR) factors with insulin secretion and sensitivity, and to determine whether the hyperbolic equilibrium of this relation is preserved in patients with rheumatoid arthritis (RA).Methods.This was a cross-sectional study encompassing 361 nondiabetic individuals: 151 with RA and 210 controls. Insulin, C-peptide, and IR indices by homeostatic model (HOMA2) were assessed. A multivariable analysis was performed to evaluate the differences in the correlation of traditional IR-related factors with glucose homeostasis molecules, as well as IR indices between patients and controls. Nonlinear regression analysis was used to assess the hyperbolic relation of insulin sensitivity and secretion.Results.HOMA2-IR indices were higher in patients with RA than controls. Hepatic insulin extraction, as assessed by the insulin:C-peptide molar ratio, was lower in patients with RA after multivariable analysis (0.08 ± 0.02 vs 0.14 ± 0.07, p < 0.001). Traditional IR-related factors showed significantly lower adjusted correlation coefficients with IR indices in patients with RA. The association between insulin sensitivity and secretion showed a different hyperbolic relation in patients with RA: the variability explained by the curve was lower in RA (nonlinear r2= 0.845 vs r2= 0.928, p = 0.001) and β coefficients (−0.74, 95% CI −0.77 to −0.70 vs −1.09, 95% CI −1.17 to −1.02, ng/ml, p < 0.001) were different in RA.Conclusion.The traditional factors associated with IR in healthy individuals are less related to IR in patients with RA. Insulin sensitivity and secretion yield a different hyperbolic equilibrium in RA.

scholarly journals Adipose Depots, Not Disease-related Factors, Account for Skeletal Muscle Insulin Sensitivity in Established and Treated Rheumatoid Arthritis

2014 ◽  
Vol 41 (10) ◽  
pp. 1974-1979 ◽  
Author(s):  
Hiba AbouAssi ◽  
K. Noelle Tune ◽  
Brian Gilmore ◽  
Lori A. Bateman ◽  
Gary McDaniel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Physical Activity ◽  
Skeletal Muscle ◽  
Body Composition ◽  
Insulin Sensitivity ◽  
Systemic Inflammation ◽  
Geometric Mean ◽  
Related Factors ◽  
Intravenous Glucose ◽  
Skeletal Muscle Insulin Sensitivity

Objective.In prior reports, individuals with rheumatoid arthritis (RA) exhibited increased insulin resistance. However, those studies were limited by either suboptimal assessment methods for insulin sensitivity or a failure to account for important determinants such as adiposity and lack of physical activity. Our objectives were to carefully assess, compare, and determine predictors of skeletal muscle insulin sensitivity in RA, accounting for adiposity and physical activity.Methods.Thirty-nine individuals with established (seropositive or erosions) and treated RA and 39 controls matched for age, sex, race, body mass index, and physical activity underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity. Inflammation, body composition, and physical activity were assessed with systemic cytokine measurements, computed tomography scans, and accelerometry, respectively. Exclusions were diabetes, cardiovascular disease, medication changes within 3 months, and prednisone use over 5 mg/day. This investigation was powered to detect a clinically significant, moderate effect size for insulin sensitivity difference.Results.Despite elevated systemic inflammation [interleukin (IL)-6, IL-18, tumor necrosis factor-α; p < 0.05 for all], persons with RA were not less insulin sensitive [SIgeometric mean (SD): RA 4.0 (2.4) vs control 4.9 (2.1)*10−5min−1/(pmol/l); p = 0.39]. Except for visceral adiposity being slightly greater in controls (p = 0.03), there were no differences in body composition or physical activity. Lower insulin sensitivity was independently associated with increased abdominal and thigh adiposity, but not with cytokines, disease activity, duration, disability, or disease-modifying medication use.Conclusion.In established and treated RA, traditional risk factors, specifically excess adiposity, play more of a role in predicting skeletal muscle insulin sensitivity than do systemic inflammation or other disease-related factors.

Role of nuclear receptors in the modulation of insulin secretion in lipid-induced insulin resistance

2008 ◽  
Vol 36 (5) ◽  
pp. 891-900 ◽  
Author(s):  
Mary C. Sugden ◽  
Mark J. Holness
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Nuclear Receptors ◽  
Feedback Loop ◽  
Farnesoid X Receptor ◽  
Lipid Lowering ◽  
Whole Body ◽  
Glucose Disposal ◽  
Healthy Individuals

In healthy individuals, a hyperbolic relationship exists between whole-body insulin-sensitivity and insulin secretion. Thus, for any difference in insulin-sensitivity, a reciprocal proportionate change occurs in insulin secretion. Such a feedback loop is evident in healthy individuals ingesting diets high in saturated fat and in late pregnancy where, despite lipid-induced insulin resistance, glucose tolerance is maintained through augmented GSIS (glucose-stimulated insulin secretion). NRs (nuclear receptors) are members of a superfamily of ligand-regulated and orphan transcription factors. On activation by a cognate ligand, many ligand-activated NRs recruit the RXR (retinoid X receptor) for heterodimer formation. Such NRs include the PPARs (peroxisome-proliferator-activated receptors), which are involved in lipid sensing and liporegulation. PPARs exert important lipid-lowering effects in vivo, thereby opposing the development of lipid-induced insulin resistance by relieving the inhibition of insulin-stimulated glucose disposal by muscle and lowering the necessity for augmented GSIS to counter lipid-induced insulin resistance. Long-chain fatty acids are proposed as natural PPAR ligands and some specific endogenous pathways of lipid metabolism are believed to generate PPAR agonists. Other NRs, e.g. the LXR (liver X receptor), which senses expansion of the metabolically active pool of cholesterol, and the FXR (farnesoid X receptor; NR1H4), which, like the LXR, is involved in sterol metabolism, also modulate systemic lipid levels and insulin-sensitivity. In this review, we discuss how these NRs impact insulin secretion via effects on the insulin-sensitivity–insulin secretion feedback loop and, in some cases, via direct effects on the islet itself. In addition, we discuss interactions between these nutrient/metabolite-responsive NRs and NRs that are central to the action of metabolically important hormones, including (i) the glucocorticoid receptor, critical for maintaining glucose homoeostasis in stress, inflammation and during fasting, and (ii) the thyroid hormone receptors, vital for maintenance of oxidative functions. We present data indicating that the RXR occupies a key role in directly modulating islet function and that its heterodimerization with at least two of its partners modulates GSIS.

scholarly journals Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess beta cell function in clinical studies

2004 ◽  
pp. 97-104 ◽  
Author(s):  
B Ahren ◽  
G Pacini
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Tolerance Test ◽  
Hyperbolic Function

Insulin sensitivity and insulin secretion are mutually related such that insulin resistance is compensated by increased insulin secretion. A correct judgement of insulin secretion therefore requires validation in relation to the insulin sensitivity in the same subject. Mathematical analyses of the relationship between insulin sensitivity and insulin secretion has revealed a hyperbolic function, such that the product of the two variables is constant. This product is usually called the disposition index. Several techniques may be used for its estimation such as data derived from the frequently sampled i.v. glucose tolerance test, the oral glucose tolerance test or the glucose-dependent arginine stimulation test or the euglycemic hyperinsulinemic clamp technique in combination with a test on insulin secretion. Using these techniques the compensatory increase in beta cell function in insulin resistance has been verified in obesity, in pregnancy and after glucocorticoid administration as has the defective beta cell function as the underlying cause of impaired glucose tolerance and type 2 diabetes. Similarly, combined analysis of insulin sensitivity and insulin secretion has shown a down-regulation of beta cell function in increased insulin sensitivity accompanying weight reduction in obesity and following exercise. Acknowledging this inverse relationship between insulin secretion and insulin sensitivity therefore requires estimation of both variables for correct assessment in any individual.

scholarly journals Cardiovascular risk factors and not disease activity, severity or therapy associate with renal dysfunction in patients with rheumatoid arthritis: Table 1

2009 ◽  
Vol 69 (3) ◽  
pp. 517-521 ◽  
Author(s):  
D Daoussis ◽  
V F Panoulas ◽  
I Antonopoulos ◽  
H John ◽  
T E Toms ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Uric Acid ◽  
Cardiovascular Risk ◽  
Disease Activity ◽  
Cardiovascular Risk Factors ◽  
Renal Dysfunction ◽  
Multivariable Analysis ◽  
Related Factors ◽  
Spearman Test

ObjectivesThe present study aimed to evaluate the prevalence and associations of renal dysfunction in patients with rheumatoid arthritis (RA). It specifically addressed the hypotheses that renal dysfunction in these patients may associate with the presence of insulin resistance, dyslipidaemia, uric acid levels and/or current levels of systemic inflammation.MethodsRenal function was assessed by estimated glomerular filtration rate (GFR) using the modification of diet in renal disease equation in 400 consecutive RA patients for this cross-sectional, single-centre study. Risk factors for renal dysfunction were recorded/measured in all participants. Correlations between GFR and other variables were analysed by Pearson or Spearman test as appropriate. Linear regression was used to test the independence of the associations between GFR and other variables.ResultsIn this RA patient cohort, 67.75% of patients had a reduced GFR of less than 90 ml/minute per 1.73 m2 and 12.75% had a GFR of less than 60 ml/minute per 1.73 m2. Multivariable analysis revealed significant associations between GFR and age (β = −0.370, p<0.001), female sex (β = −0.181, p=0.002), total cholesterol (β = −0.112, p=0.022), serum uric acid (SUA) (β = −0.425, p<0.001) and the presence of extra-articular disease, apart from sicca and/or nodules (β = −0.084, p=0.040).ConclusionsRenal dysfunction in RA is quite common and associates with classic cardiovascular risk factors such as advanced age and dyslipidaemia, levels of SUA and the presence of extra-articular disease. Renal dysfunction was not related to other RA-related factors including disease activity and duration, disability and past or present use of nephrotoxic medications.

Effect of 2 Liquid Nutritional Supplements for Diabetes Patients on Postprandial Glucose, Insulin Secretion, and Insulin Sensitivity in Healthy Individuals

2008 ◽  
Vol 33 (1) ◽  
pp. 67-70 ◽  
Author(s):  
Manuel González-Ortiz ◽  
Maria G. Ramos-Zavala ◽  
Roberto C. González-López ◽  
José A. Robles-Cervantes ◽  
Esperanza Martínez-Abundis
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Nutritional Supplements ◽  
Postprandial Glucose ◽  
Healthy Individuals ◽  
Diabetes Patients

Insulin secretion and insulin sensitivity in normal pregnancy and gestational diabetes mellitus

2003 ◽  
Vol 17 (2) ◽  
pp. 137-142 ◽  
Author(s):  
E. Akbay ◽  
M. B. Tıras ◽  
I. Yetkin ◽  
F. Törüner ◽  
R. Ersoy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Normal Pregnancy

scholarly journals POS0581 PERIODONTAL DISEASE IN RHEUMATOID ARTHRITIS: RESULTS FROM A COHORT AT TREATMENT WITH BIOLOGICAL, CLASSICAL AND TARGETED SYNTHETIC DMARDs

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 524.1-524
Author(s):  
R. Dos-Santos ◽  
F. Otero ◽  
E. Perez-Pampín ◽  
A. Mera Varela
Keyword(s):  
Rheumatoid Arthritis ◽  
Oral Health ◽  
Periodontal Disease ◽  
Disease Activity ◽  
Health Problem ◽  
Multivariable Analysis ◽  
Testing Time ◽  
Univariable Analysis ◽  
Clinical Attachment Loss ◽  
Attachment Loss

Background:Periodontal disease (PD) has been widely studied in the pathogenesis of rheumatoid arthritis (RA). As well, its relationship with severity and disease activity, has also been investigated with ambiguous results. It has been suggested that the improvement of oral health could enhance disease activity scores.1 PD prevalence worldwide stands around 60% in older adults (>65 years) and its frequency increases with aging.2Objectives:To asses oral health in RA patients and to identify predictors of PD in this population.Methods:Patients diagnosed of RA at treatment with biological, classical or targeted synthetic disease modifying anti-rheumatic drugs (b/cs/tsDMARDs) in the aforementioned hospital during 2020 performed a dental review with a specialized periodontal odontologist. Oral health patterns were given for all patients, following criteria of American Academy of Periodontology, and reevaluation of disease activity was made 2 months later.Clinical, demographic and treatment data were collected from participants.Univariable logistic regression was performed to identify predictors of PD. Variables with p<0.20 were selected for multivariable analysis.Stata 15.1 was used to perform statistical analysis.Results:81 patients were recruited. 82.72% were female. Mean age was 56.17 years (SD 14.15) and mean time since diagnosis was 15.58 years (SD 8.17). 25% were current or past smokers. 21 patients had comorbidities (arterial hypertension the most frequent). 66.67% were rheumatoid factor (RF) positive and 72.73% anti-citrullinated peptide autoantibody (ACPA) positive. Median erythrocyte sedimentation rate (ESR) was 12 mm (IQR 6;23) and mean C-reactive protein (CRP) was 0.48 mg/dl (SD 1.18). Mean disease activity score (DAS28-VSG) at the testing time was 2.62 (SD 1.21) and after 2 months was 2.39 (SD 0.97). 96.30% of patients were at treatment with csDMARDs, 64.20% with glucocorticoids, 96.30% with bDMARDs and 6 patients with tsDMARDs.Univariable analysis identified higher age, at least one autoantibody positive and ESR/CRP as potential predictors of medium/severe PD (p<0.20). Multivariable testing including these variables pointed out higher age, lower ESR and at least one autoantibody positive (OR 1.09 [CI95% 1.04-1.14] p=0.001, OR 0.18 [CI95% 0.04-0.95] p=0.044 and OR 0.94 [CI95% 0.88-1.00] p=0.042, respectively) as predictors of medium or severe PD (≥3 mm interdental clinical attachment loss).Univariable analysis identified higher age, the presence of any comorbidity and anti tumour-necrosis factor alpha treatment (anti-TNF) as potential predictors of severe PD (p<0.20). Multivariable testing including these variables pointed out higher age (OR 1.15 [CI95%1.02-1.30] p=0.026) as predictor of severe PD (≥5 mm interdental clinical attachment loss).Conclusion:Periodontal disease is still an extended health problem among the entire population. Its prevalence in RA is increased, therefore higher age and RF or ACPA positive are risk factors for developing severe PD. This analysis might suggest that an aggressive management of PD could implement better responses in DAS28. Also anti-TNF treatment could delimit a “penumbra” group of patients at risk of developing severe PD, where intensive manage could modify the final outcome.References:[1]C O Bingham, M Moni. Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions. Curr Opin Rheumatol. 2013;25(3):345-353.[2]P Carvajal. Periodontal disease as a public health problem: the challenge for primary health care. Rev Clin Periodoncia inplantol. 2016;9(2):177-183.Disclosure of Interests:None declared

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