Increased Insulin Resistance and Glucagon Levels in Mild/Inactive Systemic Lupus Erythematosus Patients Despite Normal Glucose Tolerance.
To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT).



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.



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).



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.
Universidade de Sao Paulo, Sao Paulo, Brazil.
Cíntia N H
CNH
Miyake
Universidade de Sao Paulo, Sao Paulo, Brazil.
Bruno
B
Gualano
Universidade de Sao Paulo, Sao Paulo, Brazil.
Wagner S
WS
Dantas
Universidade de Sao Paulo, Sao Paulo, Brazil.
Renato T
RT
Pereira
Universidade de Sao Paulo, Sao Paulo, Brazil.
William
W
Neves
Butantan Institute, Sao Paulo, Brazil.
Vanessa O
VO
Zambelli
Universidade de Sao Paulo, Sao Paulo, Brazil.
Samuel K
SK
Shinjo
Universidade de Sao Paulo, Sao Paulo, Brazil.
Rosa M
RM
Pereira
Universidade de Sao Paulo, Sao Paulo, Brazil.
Elizabeth R
ER
Silva
Universidade de Sao Paulo, Sao Paulo, Brazil.
Ana Lúcia
AL
Sá-Pinto
Universidade de Sao Paulo, Sao Paulo, Brazil.
Eduardo
E
Borba
Universidade de Sao Paulo, Sao Paulo, Brazil.
Hamilton
H
Roschel
Universidade de Sao Paulo, Sao Paulo, Brazil.
Eloisa
E
Bonfá
Universidade de Sao Paulo, Sao Paulo, Brazil.
Fabiana B
FB
Benatti
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005215:Fasting / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood*; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism; D019518:Postprandial Period; D012720:Severity of Illness Index
D015415:Biomarkers; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; C495692:SLC2A4 protein, human; D005934:Glucagon