Immune reconstitution in ART treated, but not untreated HIV infection, is associated with abnormal beta cell function

• Published in: PloS one Vol. 13; no. 5; p. e0197080
• Main Authors: Sims, Emily K, Park, Grace, Mather, Kieren J, Mirmira, Raghavendra G, Liu, Ziyue, Gupta, Samir K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.05.2018; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; Age Factors; AIDS; Anti-HIV Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active; Apoptosis; Beta cells; Biology and Life Sciences; Biomarkers; Biomarkers - blood; Blood Glucose - metabolism; Body mass; Body Mass Index; C-Peptide - blood; Care and treatment; Case-Control Studies; CD4 antigen; CD4 Lymphocyte Count; Cell death; Cell-Free Nucleic Acids - blood; Cellular stress response; Control; Deoxyribonucleic acid; Diabetes; Diabetes mellitus; DNA; Drug therapy; Fasting; Female; Glucose; Health aspects; Health risks; Highly active antiretroviral therapy; HIV; HIV infections; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - physiopathology; Homeostasis; Human immunodeficiency virus; Humans; Immune Reconstitution; Infections; Infectious diseases; Insulin; Insulin - blood; Insulin Resistance; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - immunology; Insulin-Secreting Cells - pathology; Laboratory testing; Male; Markers; Medicine; Medicine and Health Sciences; Metabolic disorders; Middle Aged; Pediatrics; Peptides; Physical Sciences; Preproinsulin; Proinsulin - blood; Protein Precursors - blood; Regression analysis; Ribonucleic acid; Risk factors; RNA; Sex Factors; Sexually transmitted diseases; Smoking; Smoking - physiopathology; STD; Stress; Stresses; Toxicity; Type 2 diabetes; Viral infections; Viruses; Indiana; United States > US; Indianapolis Indiana
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0197080

HIV infection has been associated with increased diabetes risk, but prior work has mostly focused on insulin resistance, as opposed to beta cell effects, or included patients on antiretroviral therapies (ART) directly linked to metabolic toxicity. In this analysis, we measured markers of glucose homeostasis and beta cell function, stress, and death in fasting sera from a cross section of HIV+ individuals off ART (n = 43), HIV+ individuals on ART (n = 23), and HIV- controls (n = 39). Markers included glucose, HOMA%S, HOMA%B, proinsulin:C-peptide ratio (PI:C ratio), and circulating preproinsulin (INS) DNA. We performed multiple linear regressions with adjustments for age, sex, race, BMI, and smoking status. Compared to HIV- controls, HIV+ participants off ART exhibited similar beta cell function and insulin sensitivity, without increases in markers of beta cell stress or death. Specifically, in HIV+ participants with CD4 counts <350 cells/μL, PI:C ratios were lower than in HIV- controls (p<0.01), suggesting a reduction in intrinsic beta cell stress among this group. By contrast, HIV+ participants on ART had higher fasting glucose (p<0.0001) and lower HOMA%B (p<0.001) compared to HIV- controls. Among the entire HIV+ population, higher HIV RNA correlated with lower fasting glucose (r = -0.57, p<0.001), higher HOMA%B (r = 0.40, p = 0.001), and lower PI:C ratios (r = -0.42, p<0.001), whereas higher CD4 counts correlated with higher PI:C ratios (r = 0.2, p = 0.00499). Our results suggest that HIV seropositivity in the absence of ART does not worsen beta cell function or glucose homeostasis, but immune reconstitution with ART may be associated with worsened beta cell function.