c-peptide and Lupus-Erythematosus--Systemic

Systemic lupus erythematosus (SLE) has been associated with insulin resistance and beta-cell dysfunction. Apolipoprotein C3 (ApoC3) is a component of very low-density lipoproteins. Since ApoC3 has been linked to beta-cell impairment in the general population, in this study we aimed to discover if this lipoprotein is related to glucose homeostasis disturbance in patients with SLE.. One hundred and forty non diabetic patients with SLE who had a glycaemia 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 to those molecules and indices adjusting for classical factors associated with insulin resistance that included glucocorticoids.. In the multivariable regression analysis that included prednisone intake, a significant relation of ApoC3 to C-peptide was found (beta coef. 0.27 [95%CI 0.03-0.51) ng/ml, p=0.030). Similarly, ApoCa3 was associated with higher degree of beta-cell dysfunction (HOMA2-%B) although in this case statistical significance was not achieved (beta coef. 8 [95%CI-1-18], p=0.086). This relationship was not found with serum insulin levels or IR indices. Furthermore, in the univariable analysis, but not after multivariable adjustment, the disease damage score was found to significantly mediate the effect of ApoC3 on circulating C-peptide. and HOMA2-%B.. Beta-cell dysfunction and ApoC3 are linked in patients with SLE.

Topics: Apolipoprotein C-III; C-Peptide; Humans; Insulin; Insulin Resistance; Lupus Erythematosus, Systemic

To investigate how markers of beta-cell secretion (proinsulin-processing metabolites) are expressed in SLE patients and their potential relation to features associated with the disease such as activity or damage.. One hundred and forty-four SLE patients and 69 nondiabetic sex- and age-matched controls were assessed. Beta-cell secretion molecules, as measured by insulin, split and intact proinsulins, and C-peptide levels were analysed in both groups. Multiple regression analysis was performed to compare proinsulin propeptides between groups and to explore the interrelations with SLE features. Analyses were adjusted for glucocorticoid intake and for insulin resistance classic risk factors.. Fully multivariable analysis demonstrated that regardless of glucocorticoid use, SLE patients exhibited higher levels of split proinsulin. Likewise, the split proinsulin-to-insulin ratio was upregulated in patients with SLE undergoing glucocorticoid therapy [beta coeficient 0.19 (95% Confidence Interval 0.07, 0.30), P = 0.002] or not [beta coef. 0.09 (95% CI: 0.01, 0.17), P = 0.025]. Similar results were found for the intact proinsulin-to-insulin ratio, although differences were only statistically significant for patients taking glucocorticoids [beta coef. 0.08 (95% CI: 0.03, 0.12), P = 0.001]. SLE damage score was associated with higher serum levels of intact [beta coef. 0.51 (95% CI 0.17, 0.86) pmol/l, P = 0.004] and split proinsulins [beta coef. 1.65 (95% CI 0.24, 3.06) pmol/l, P = 0.022] after multivariable analysis, including disease duration and prednisone use.. Among patients with SLE, proinsulin-processing metabolites, a marker of beta-cell disruption, are upregulated compared with matched controls. This disproportionate hyperproinsulinemia can be explained by the damage produced by the disease and occurs independently of prednisone use.

Topics: Adult; C-Peptide; Diabetes Mellitus; Female; Glucocorticoids; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Lupus Erythematosus, Systemic; Male; Middle Aged; Proinsulin

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of immunologic self-tolerance and the subsequent development of autoantibodies. These antibodies are thought to be important in relation to the clinical manifestations of the disease. One example is the development of multiple cytopenias secondary to cytolytic or cytotoxic antibodies directed toward red blood cells, platelets, and white blood cells. Other antibodies may mediate abnormal cellular mechanisms such as those seen with neuropsychiatric manifestations of SLE. We report the occurrence of autoantibodies directed toward insulin receptors and the subsequent development of type B insulin resistance syndrome in a woman with SLE. This syndrome was treated successfully with cyclophosphamide and mycophenolate mofetil.

Topics: Adult; C-Peptide; Cyclophosphamide; Female; Glycated Hemoglobin; Humans; Hyperinsulinism; Immunosuppressive Agents; Insulin; Insulin Resistance; Lupus Erythematosus, Systemic; Mycophenolic Acid; Treatment Outcome

Topics: Acanthosis Nigricans; C-Peptide; Female; Humans; Hyperinsulinism; Insulin Resistance; Lupus Erythematosus, Systemic; Middle Aged; Syndrome

We studied a patient with systemic lupus erythematosus and type B insulin resistance, who progressed from extreme insulin resistance to fasting hypoglycemia. The plasma insulin level was 63.3 +/- 20.9 pmol/L in the fasting state and rose above 1440 pmol/L postprandially. Intravenous administration of human insulin caused almost no decline in plasma glucose. Therefore, it was concluded that the patient was still resistant to insulin and that plasma insulin did not play a crucial role in the development of hypoglycemia. Immunoglobulin G from this patient did not inhibit insulin binding to the insulin receptor; rather, it enhanced [125I]insulin binding in both the immunoprecipitate and the in vitro binding assay to intact cells. Antiinsulin receptor antibodies strongly inhibited insulin internalization in human adipocytes, slowed down the dissociation of [125I]insulin from receptors and failed to induce down-regulation of surface insulin receptors in both the presence and absence of insulin. Finally, autoantibodies mimicked the insulin stimulatory effect on human fat cell lipogenesis even after long term exposure, but inhibited the metabolic potency of insulin when added simultaneously with the natural ligand. We conclude that antiinsulin receptor antibodies induce fasting hypoglycemia, through their continuous receptor stimulatory action, and insulin resistance, possibly by a conformational perturbation of the receptor protein, which, in turn, uncouples insulin receptor binding from receptor function.

Topics: Antibodies; Blood Cells; Blood Glucose; C-Peptide; Down-Regulation; Female; Humans; Hypoglycemia; Immunoglobulin G; Injections, Intravenous; Insulin; Insulin Resistance; Lipid Metabolism; Lupus Erythematosus, Systemic; Middle Aged; Precipitin Tests; Receptor, Insulin