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

Arthritis Care Res (Hoboken). 2018 Jan;70(1):114-124. doi: 10.1002/acr.23237. Epub 2017 Dec 6.


Objective: To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT).

Methods: In 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.

Results: SLE 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).

Conclusion: We 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Glucose / metabolism*
  • Case-Control Studies
  • Cross-Sectional Studies
  • Fasting / blood
  • Female
  • Glucagon / blood*
  • Glucose Tolerance Test
  • Glucose Transporter Type 4 / metabolism
  • Humans
  • Insulin / blood*
  • Insulin Resistance*
  • Insulin-Secreting Cells / metabolism
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / physiopathology
  • Muscle, Skeletal / metabolism
  • Postprandial Period
  • Severity of Illness Index


  • Biomarkers
  • Blood Glucose
  • Glucose Transporter Type 4
  • Insulin
  • SLC2A4 protein, human
  • Glucagon