Increased Insulin Resistance and Glucagon Levels in Mild/Inactive Systemic Lupus Erythematosus Patients Despite Normal Glucose Tolerance

Author(s):Show less -

Miyake, Cintia N. H. ^[1] ; Gualano, Bruno ^[1] ; Dantas, Wagner S. ^[1] ; Pereira, Renato T. ^[1] ; Neves, William ^[1] ; Zambelli, Vanessa O. ^[2] ; Shinjo, Samuel K. ^[1] ; Pereira, Rosa M. ^[1] ; Silva, Elizabeth R. ^[1] ; Sa-Pinto, Ana Lucia ^[1] ; Borba, Eduardo ^[1] ; Roschel, Hamilton ^[1] ; Bonfa, Eloisa ^[1] ; Benatti, Fabiana B. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med FMUSP, Sao Paulo - Brazil

^[2] Butantan Inst, Sao Paulo - Brazil

• Document type: Journal article
• Source: ARTHRITIS CARE & RESEARCH; v. 70, n. 1, p. 114-124, JAN 2018.
• Web of Science Citations: 4

Abstract

ObjectiveTo assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT). MethodsIn this cross-sectional study, 33 adult females with mild/inactive SLE (SLE group) and 16 age- and body mass index-matched female healthy controls (CTRL group) underwent an MTT and were assessed for insulin sensitivity and beta cell function. Skeletal muscle protein expressions of total and membrane insulin-dependent glucose transporter 4 (GLUT-4) were also evaluated (SLE group: n = 10, CTRL group: n = 5); muscle biopsies were performed after MTT. Further measurements included inflammatory cytokines, adipocytokines, physical activity level, body composition, and food intake. ResultsSLE and CTRL groups showed similar fasting glucose, glucose response, and skeletal muscle GLUT-4 translocation after MTT. However, the SLE group demonstrated higher fasting insulin levels (P = 0.01; effect size {[}ES] 1.2), homeostatic model assessment insulin resistance (IR) (P = 0.03; ES 1.1), insulin-to-glucose ratio response to MTT (P = 0.02; ES 1.2), fasting glucagon levels (P = 0.002; ES 2.7), glucagon response to MTT (P = 0.0001; ES 2.6), and a tendency toward lower Matsuda index of whole-body insulin sensitivity (P = 0.06; ES -0.5) when compared with the CTRL group. Fasting proinsulin-to-insulin ratio and proinsulin-to-insulin ratio response to MTT were similar between groups (P > 0.05), while the SLE group showed a higher insulinogenic index when compared with the CTRL group (P = 0.02; ES = 0.9). ConclusionWe have identified that SLE patients had a bi-hormone metabolic abnormality characterized by increased IR and hyperglucagonemia despite normal glucose tolerance and preserved beta cell function and skeletal muscle GLUT-4 translocation. Strategies capable of ameliorating insulin sensitivity to reduce the risk of type 2 diabetes mellitus and cardiovascular disease in SLE may require more than targeting IR alone. (AU)

• FAPESP's process: 11/24093-2 - The effects of endurance exercise on the inflammatory profile and insulin sensitivity in women with systemic lupus erithematosus
• Grantee: Eloisa Silva Dutra de Oliveira Bonfá
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/08302-0 - Effects of chronic aerobic training on the insulin sensitivity of patients with systemic lupus erythematosus
• Grantee: Fabiana Braga Benatti
• Support Opportunities: Scholarships in Brazil - Post-Doctoral