c-peptide and Arthritis--Rheumatoid

To investigate the dose-related effects of glucocorticoid treatment on glucose tolerance, beta cell function, and insulin sensitivity in patients with early active rheumatoid arthritis (RA).. A randomized, controlled, single-blind trial was conducted in 41 patients with early active RA. At the beginning of the trial patients had not been treated for their RA, and were randomized to begin treatment with prednisolone at 60 mg/day or 30 mg/day. Before and at the end of 1 week of treatment, a frequently sampled oral glucose tolerance test was performed. The glucose area under the curve (AUC(G) ) was calculated. In addition, beta cell function and insulin sensitivity parameters were computed.. Patients (mean ± SD age 55.5 ± 14.8 years and 54.2 ± 12.6 years in the prednisone 60 mg/day and prednisone 30 mg/day groups, respectively; body mass index 24.5 ± 4.1 kg/m(2) and 25.4 ± 4.2 kg/m(2) , respectively) had active disease at baseline (mean ± SD Disease Activity Score in 44 joints 4.1 ± 0.7 and 4.0 ± 0.8, respectively; median C-reactive protein [CRP] level 14 mg/liter [interquartile range 6-34] and 19 mg/liter [interquartile range 3-39], respectively). In addition, 56% of the patients had impaired glucose tolerance at baseline, and 7% were found to have previously unrecognized type 2 diabetes mellitus (DM). Associations of the AUC(G) with erythrocyte sedimentation rate (β = 2.430 [95% confidence interval 0.179-4.681], P = 0.04) and with CRP level (β = 2.358 [95% confidence interval 0.210-4.506], P = 0.03) were demonstrated. Treatment with prednisolone at both dosages reduced CRP levels significantly. The incidence of type 2 DM increased to 24% (P < 0.001) (evenly distributed across the groups). The mean AUC(G) did not change in either treatment arm. Beta cell function improved during prednisone treatment at 60 mg/day (P = 0.02) and at 30 mg/day (P = 0.04). Disease duration was associated with changes in the AUC(G) (β = 3.626 [95% confidence interval 1.077-6.174], P = 0.007) and with deterioration of the glucose state (odds ratio 1.068 [95% confidence interval 1.017-1.122], P = 0.009).. In this study, short-term treatment with prednisolone 60 mg or 30 mg per day improved disease activity without deterioration of glucose tolerance in patients with active RA. However, due to individual differences, monitoring is recommended.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Early Diagnosis; Female; Glucocorticoids; Glucose Tolerance Test; Health Status; Humans; Inflammation; Insulin Resistance; Joints; Male; Middle Aged; Prednisolone; Severity of Illness Index

Insulin resistance and beta-cell dysfunction are manifestations of rheumatoid arthritis (RA). Apolipoprotein C-III (ApoC3) has been associated with such insulin resistance and beta-cell dysfunction in the general population. Our purpose was to study whether ApoC3 is also related to the insulin resistance and beta-cell dysfunction that are present in patients with RA.. Three hundred thirty-eight non-diabetic patients with RA who had a glycemia lower than 110 mg/dl were recruited. Insulin, C-peptide, and ApoC3 were assessed. Insulin resistance and beta-cell function were calculated using the Homeostasis Model Assessment (HOMA2) indices. A multivariable regression analysis was performed to study the relationship of ApoC3 with those molecules and indices adjusting for classic factors associated with insulin resistance that included glucocorticoids.. ApoC3 was related to significant higher levels of circulating insulin (beta coef. 0.37 [95%CI 0.01-0.73] µU/ml, p = 0.044) and C-peptide (beta coef. 0.13 [95%CI 0.05-0.22] ng/ml, p = 0.003), and higher insulin resistance -HOMA2-IR- (beta coef. 0.05 [95%CI 0.00-0.09], p = 0.041) and beta-cell dysfunction -HOMA2-%B- (beta coef. 2.94 [95%CI 0.07-5.80], p = 0.044) indices. This was found after a fully multivariable analysis that included, among others, prednisone intake and the classic factors associated with carbohydrate metabolism such as triglycerides, waist circumference, and obesity.. ApoC3, insulin resistance, and beta-cell dysfunction are independently associated in patients RA.

Topics: Apolipoprotein C-III; Arthritis, Rheumatoid; C-Peptide; Humans; Insulin; Insulin Resistance

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).. 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.. 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.

Topics: Adult; Aged; Arthritis, Rheumatoid; Blood Glucose; C-Peptide; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged

A recent study in rheumatoid arthritis (RA) patients using electrical vagus nerve stimulation (VNS) to activate the inflammatory reflex has shown promising effects on disease activity. Innervation by the autonomic nerve system might be involved in the regulation of many endocrine and metabolic processes and could therefore theoretically lead to unwanted side effects. Possible effects of VNS on secretion of hormones are currently unknown. Therefore, we evaluated the effects of a single VNS on plasma levels of pituitary hormones and parameters of postprandial metabolism. Six female patients with RA were studied twice in balanced assignment (crossover design) to either VNS or no stimulation. The patients selected for this substudy had been on VNS therapy daily for at least 3 months and at maximum of 24 months. We compared 10-, 20-, and 30-min poststimulus levels to baseline levels, and a 4-h mixed meal test was performed 30 min after VNS. We also determined energy expenditure (EE) by indirect calorimetry before and after VNS. VNS did not affect pituitary hormones (growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, follicle-stimulating hormone, and luteinizing hormone), postprandial metabolism, or EE. Of note, VNS reduced early postprandial insulin secretion, but not AUC of postprandial plasma insulin levels. Cortisol and catecholamine levels in serum did not change significantly. Short stimulation of vagal activity by VNS reduces early postprandial insulin secretion, but not other hormone levels and postprandial response. This suggests VNS as a safe treatment for RA patients.

Topics: Adrenocorticotropic Hormone; Adult; Arthritis, Rheumatoid; C-Peptide; Calorimetry, Indirect; Cross-Over Studies; Energy Metabolism; Female; Follicle Stimulating Hormone; Human Growth Hormone; Humans; Luteinizing Hormone; Middle Aged; Postprandial Period; Prolactin; Thyrotropin; Vagus Nerve Stimulation

C-peptide has pro-atherogenic effects in animal models, and elevated C-peptide levels are associated with cardiovascular and all-cause mortality in patients undergoing coronary angiography. This cross-sectional study investigated the association between C-peptide serum levels and coronary artery calcification (CAC) in patients with rheumatoid arthritis (RA), a high-risk group for cardiovascular events. Fifty-four patients with RA were recruited from an arthritis outpatient department at the University Hospital in Aachen, Germany. CAC was measured by multi-slice CT scan, and blood samples were drawn from all patients for the analysis of C-peptide and other cardiovascular biomarkers. Mean serum levels of C-peptide (1.187 ± 0.771 vs 0.745 ± 0.481 nmol/L, p = 0.02), YKL-40, LDL cholesterol, and triglycerides were significantly higher in patients with CAC (n = 32, 59 %) compared to those without CAC (n = 22, 41 %). Univariate analysis revealed a significant association of C-peptide [OR 4.7, 95 % CI (1.1, 20.2)], YKL-40, triglycerides, hypertension, smoking, age, and male sex with the presence of CAC. After adjustment for body mass index, cholesterol, diabetes, adiponectin, calcium, and phosphate, C-peptide was still significantly associated with CAC in a multivariate logistic regression model. In conclusion, C-peptide serum levels are independently associated with the presence of CAC in patients with RA. These data suggest a potential role of C-peptide in cardiovascular disease in patients with RA.

Topics: Aged; Arthritis, Rheumatoid; C-Peptide; Calcinosis; Cholesterol, LDL; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Triglycerides

Local effects of hormones on immune and connective tissues could play some role in the development of local inflammation processes. The aim of this study was to investigate the levels of selected hormones in pleural exudates of patients with pleurisy and lung tumours, and compare these levels with hormone concentration in knee synovial fluid.. Eleven patients with pleural exudate (mean age 62+/-3) and l9 subjects with rheumatoid arthritis (of the same mean age) participated in the observations. Plasma, pleural exudates and synovial fluid levels of cortisol, prolactin, aldosterone, testosterone, 17-beta-estradiol, dehydroepiandrosterone, progesterone, insulin and C-peptide were determined by specific radioimmunoassay.. It was noted that all estimated hormones are transferred into pleural exudates and synovial fluid. Higher levels of dehydroepiandrosterone and C-peptide were observed in pleural exudates as compared to plasma. The concentrations of testosterone, prolactin and estradiol in males were lower in exudates as compared to plasma. Mean levels of cortisol, aldosterone, progesterone and insulin in plasma were similar to these found in pleural exudates. The comparison of hormone levels in pleural exudates and synovial fluid showed that the levels of cortisol, progesterone and dehydroepiandrosterone tended to be higher in the exudates as compared to synovial fluid. However, the levels of insulin, testosterone and estradiol in exudates were lower than these in inflammatory synovial fluid from patients with rheumatoid arthritis.. This study showed the presence of hormones in pleural exudates. The differences in hormone concentrations in pleural exudates and synovial fluid were observed suggesting a specificity of hormone transfer from plasma to these exudates.

Topics: Aged; Aldosterone; Arthritis, Rheumatoid; C-Peptide; Dehydroepiandrosterone; Estradiol; Exudates and Transudates; Female; Hormones; Humans; Hydrocortisone; Insulin; Knee Joint; Male; Middle Aged; Pleural Effusion; Pleurisy; Progesterone; Prolactin; Radioimmunoassay; Synovial Fluid; Testosterone

Hormones other than adrenal and gonadal steroids may play also a significant role in the pathogenesis of rheumatoid arthritis. The aim of this study was to investigate the levels of selected peptide hormones and histamine in synovial fluid of knee joints and in plasma of patients with rheumatoid arthritis and with osteoarthrosis.. The concentrations of insulin, C-peptide, prolactin, growth hormone, free triiodothyronine (FT3), thyrotropin (TSH), and histamine were determined in synovial fluid and plasma of 27 patients with rheumatoid arthritis (RA) and in 12 patients with osteoarthrosis (OA).. The presence of peptide hormones in synovial fluid was demonstrated. The levels of TSH and growth hormone were lower in synovial fluid than in plasma in both groups, while those of prolactin were comparable in synovial fluid and in plasma. The levels of C-peptide (p < 0.05), insulin and FT3 were higher in synovial fluid than in plasma of OA patients, but lower in synovial fluid of RA patients as compared to their levels in plasma. Significant positive correlations between the levels in plasma and synovial fluid were observed in prolactin (p < 0.001, r = 0.741) and TSH (p < 0.05, r = 0.88) only. After age adjustment, no significant differences in synovial fluid and in plasma levels of all hormones were found between OA and RA patients. The levels of histamine in plasma were similar in RA and OA patients, in synovial fluid of both groups histamine was found in almost undetectable amounts.. The selected peptide hormones, e.g. insulin, C-peptide, prolactin, growth hormone, FT3 and TSH, are present in synovial fluid of RA and OA patients, some of them in the concentrations comparable to these in plasma. The role of the locally present hormones in pathogenesis of RA has to be investigated in further studies and analyses.

Topics: Arthritis, Rheumatoid; C-Peptide; Female; Histamine; Human Growth Hormone; Humans; Insulin; Knee Joint; Male; Middle Aged; Osteoarthritis; Peptide Hormones; Prolactin; Synovial Fluid; Thyrotropin; Triiodothyronine

Although it is well known that patients with type 1 diabetes mellitus are susceptible to other autoimmune diseases, the simultaneous occurrence of clustered distinct autoimmune diseases is uncommon. We report a 16-year-old girl, previously diagnosed as having coeliac disease and IgA deficiency, who at 13 years of age developed a clustering of distinct autoimmune diseases, including type 1 diabetes mellitus, rheumatoid arthritis (RA) and euthyroid autoimmune thyroiditis, eventually resulting in a simultaneous long-term remission. The clinical picture was associated with a functional immunodeficiency characterized by a defect in proliferative responses to T cell predominant mitogens and a normal response to the B cell predominant mitogen. In addition, the T cell activation markers HLA-DR, IL-2 receptor and transferrin receptor) were not upregulated. The clinical course of this immunodeficiency paralleled the outcome of the autoimmune diseases. After the abrupt onset, spontaneous clinical remission of both diabetes mellitus and RA was observed. Insulin was first reduced in dose and then discontinued completely at 15 months, in the presence of normal C peptide secretion and normal metabolic control (HbA1c 5.8%). Anti-glutamate decarboxylase (GAD65) and anti-IA-2 antibodies remained persistently high. During the remission phase a normalization of the functional immune defect was observed. The gradual resolution of the multisystemic diseases as well as the normalization of immune function in our patient is unusual. This case may be of considerable value in furthering our knowledge of the immunological mechanisms implicated in these rare multireactive syndromes.

Topics: Adolescent; Arthritis, Rheumatoid; Autoantibodies; C-Peptide; Celiac Disease; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Female; Glucose Tolerance Test; Humans; IgA Deficiency; Mitogens; Remission, Spontaneous; Thyroiditis, Autoimmune; Up-Regulation

Recent evidence suggests that hyperinsulinemia may contribute to the development of various risk factors of atherosclerosis. To examine the effects of energy intake on insulin secretion, 24-h urine C-peptide was measured in twelve women with rheumatoid arthritis who were not taking any medicine and stayed in Koda hospital for a diet therapy which lasted 55 days. They were basically placed on a 1200 kcal/day vegan diet combined with three 3-5-day fasting periods (200 kcal/day). Urine C-peptide excretion markedly decreased from 31-40 to 8-14 micrograms/day during the fasting periods. Among the anthropometric variables examined, the average level of urine C-peptide excretions measured in the fasting periods showed a significant correlation with the percentage and the amount of body fat. However, such correlation was not observed while the calorie intake was 1200 kcal. No clinical laboratory parameter showed a significant correlation with urinary C-peptide excretion. These results suggest that the major determinant of urine C-peptide excretion is food intake and that hyperinsulinemia could be easily improved by restricting energy intake.

Topics: Arthritis, Rheumatoid; C-Peptide; Energy Intake; Female; Humans; Hyperinsulinism

Glucose metabolism was studied after an intravenous glucose loading in normal-weighted, previously untreated patients (n = 14) with active rheumatoid arthritis (RA). The patients displayed an enhanced insulin response and impaired glucose handling compared with healthy controls (P less than .001). The insulin sensitivity, measured as the glucose utilization rate during steady state of euglycemia (M) was significantly decreased (P less than .01) among the patients compared to the controls (5.5 +/- 1.9 mg/kg BW/min [mean +/- SD] and 7.2 +/- 1.2, respectively). The corresponding values for the metabolic clearance rate (MCR) were 5.8 +/- 0.6 mL/kg BW/min and 8.2 +/- 0.4, respectively (P less than .01). In the patient group the k value correlated with the peripheral insulin sensitivity (P less than .01), which, in turn, was inversely related to the acute phase reaction (P less than .05). During 1 week of potent anti-inflammatory treatment with corticosteroids (prednisolone 20 mg daily) the k value improved P less than .001), the insulin sensitivity tended to improve and the insulin response increased (P less than .001) after an intravenous glucose loading. Five patients who had a remission of their disease on sulphasalazine as antirheumatic therapy were reexamined. A normalization of the inflammatory activity as well as the glucose handling and insulin sensitivity was achieved. The data obtained indicate that impaired glucose handling in active RA is related to insulin resistance. The linkage between inflammatory indices and glucose metabolism might reflect a special consequence of inflammation, but the influence of nonspecific disease manifestations, ie, malnutrition, inactivity, and myopenia, has to be considered.

Topics: Adrenal Cortex Hormones; Adult; Aged; Arthritis, Rheumatoid; Blood Glucose; C-Peptide; Female; Humans; Insulin Resistance; Male; Middle Aged; Sulfasalazine

Since and adverse effect of chloroquine (Cq) on the specific functions of the pancreatic beta-cell has been recently documented in animals, it was of interest to study if a similar effect could be demonstrated during Cq treatment in homo. The effect of Cq on glucose tolerance and insulin secretion was studied in 10 patients with rheumatoid arthritis (RA) over a 3-month period. Fasting plasma levels of glucose, insulin, C-peptide and glucosylated haemoglobin (HbA1c) were checked before starting treatment, after 3 months' Cq treatment and 3 months after withdrawal of treatment. At the same intervals oral glucose tolerance tests (OGTT) were performed. No significant change in any of these parameters was found during treatment with Cq. In patients with a normal OGTT, Cq inhibition of insulin synthesis and/or secretion cannot be demonstrated, as measured by a decreased plasma insulin an C-peptide response to oral glucose load.

Topics: Adult; Aged; Arthritis, Rheumatoid; Blood Glucose; C-Peptide; Chloroquine; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Peptides

Twenty five cases of insulin autoimmune syndrome including this case has been reported so far without having the pathogenesis clarified. This paper describes a case which suggests one aspect of pathogenesis. The patient, a housewife concurrently had insulinoma and severe rheumatoid arthritis, complaining of hypoglycemic syncope attacks. During the attacks her blood sugar levels ranged from 19 to 22 mg%. Her serum extractable immunoreactive insulin (IRI) and insulin binding antibody levels were 557 microunits/ml and 0.390 mU/ml, respectively. gamma-Globulin-bound insulin was also measured electrophoretically. Bio-Gel P 10 column chromatography eluted almost all IRI at the void volume at pH 7.4 and a smaller but significant IRI peak also at pH 3.0. Selective angiography revealed a tumor-like staining in the pancreas body. Pancreatectomy relieved her of hypoglycemic attacks. Histology disclosed two small insulinomas. Insulinoma, rheumatoid arthritis and insulin autoimmune syndrome coexisted in this case, suggesting some causal relationship among them.

Topics: Adenoma, Islet Cell; Arginine; Arthritis, Rheumatoid; Autoimmune Diseases; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Antibodies; Middle Aged; Pancreatectomy; Pancreatic Neoplasms