Sitagliptin Reduces Inflammation and Chronic Immune Cell Activation in HIV+ Adults With Impaired Glucose Tolerance.
BACKGROUND
HIV infection is associated with a greater risk for fasting hyperinsulinemia, impaired glucose tolerance, and higher incidence rates for vascular disease, myocardial infarction, or stroke despite effective combination antiretroviral therapy (cART). The underlying mechanism(s) may involve chronic low-grade systemic inflammation and immune cell activation. Dipeptidyl peptidase-4 inhibitors (sitagliptin) improve glucose tolerance and may possess immunomodulatory effects because leukocyte CD26 cell surface receptors express dipeptidyl peptidase-4 activity.


OBJECTIVE
Sitagliptin will reduce inflammatory and immune cell activation markers known to be elevated in cART-treated HIV-infected (HIV+) adults with impaired glucose tolerance.


METHODS
This was designed as a prospective, randomized, placebo-controlled, double-blind trial of sitagliptin in HIV+ adults.


METHODS
The setting was an academic medical center.


METHODS
Patients were cART-treated HIV+ men and women (n = 36) with stable HIV disease and impaired glucose tolerance.


METHODS
Interventions included sitagliptin 100 mg/d or placebo for 8 weeks.


METHODS
At baseline and week 8, plasma high-sensitivity C-reactive protein and C-X-C motif chemokine 10 concentrations (ELISA), oral glucose tolerance, and abdominal sc adipose mRNA expression for M1 macrophage markers (monocyte chemotactic protein-1, EGF-like module-containing, mucin-like hormone receptor 1).


RESULTS
Sitagliptin reduced glucose area under the curve (P = .002) and improved oral glucose insulin sensitivity index (P = .04) more than placebo. Sitagliptin reduced plasma high-sensitivity C-reactive protein and C-X-C motif chemokine 10 levels more than placebo (P < .009). Adipose tissue monocyte chemotactic protein-1 mRNA abundance declined significantly more (P = .01), and adipose EGF-like module-containing, mucin-like hormone receptor 1 mRNA expression tended to decline more (P = .19) in sitagliptin than placebo.


CONCLUSIONS
Sitagliptin had beneficial systemic and adipose anti-inflammatory effects in cART-treated HIV+ adults with impaired glucose tolerance. Large-scale, long-term studies should determine whether sitagliptin reduces cardiovascular risk and events in HIV+ adults.
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Conor
C
Best
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Heidi
H
Struthers
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Erin
E
Laciny
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Michael
M
Royal
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Dominic N
DN
Reeds
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Kevin E
KE
Yarasheski
D054392:Adipokines / Q000097:blood; D000328:Adult; D018925:Chemokines / Q000097:blood; D066026:Endothelial Progenitor Cells / Q000473:pathology; D005260:Female; D018149:Glucose Intolerance / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use*
D054392:Adipokines; D018925:Chemokines; D007004:Hypoglycemic Agents; D011719:Pyrazines; D014230:Triazoles; D000068900:Sitagliptin Phosphate