Abstract
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.
Highlights
The development and success of combination antiretroviral therapy (ART) has transformed the prognosis of individuals infected with Human Immunodeficiency Virus (HIV), effectively increasing lifespans to approaching those of HIV-uninfected individuals [1,2,3]
Associations between HIV seropositivity and diabetes have been previously described, the innate contribution of HIV infection on glucose homeostasis is not clear. Previous studies on this topic are complicated by inclusion of individuals receiving ART regimens containing the thymidine analogs stavudine and didanosine and first-generation protease inhibitors, which have been independently implicated in lipodystrophy and development of diabetes in HIV, or have focused on insulin resistance rather than beta cell function
We analyzed a cross-section of serum samples from HIV+ individuals that were not receiving HIV-related therapy, and individuals that had achieved viral suppression on more modern and less metabolically active ART regimens
Summary
The development and success of combination antiretroviral therapy (ART) has transformed the prognosis of individuals infected with Human Immunodeficiency Virus (HIV), effectively increasing lifespans to approaching those of HIV-uninfected individuals [1,2,3]. These successes have brought about a simultaneous evolution in the epidemiology of the HIV positive population, with an emergence of numerous medical comorbidities associated with chronic HIV infection [4]. Similar to T2D, HIV infected patients developing diabetes typically present with a relative insulin deficiency associated with increased peripheral insulin resistance and may respond to treatment with oral diabetes medications [11]. While T2D is typified by beta cell dysfunction, the potential contribution of beta cell dysfunction to HIV-related DM remains much less characterized [15]
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