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Inflammatory markers associated with development of diabetes in people taking HIV therapy
Michael Carter, 2014-10-20 09:00:00
elevations in important markers of systemic inflammation are associated with
the development of type-2 diabetes in people taking antiretroviral therapy
(ART), investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The authors
examined the relationship between baseline levels of high sensitivity
C-reactive protein (hsCRP) and interleukin-6 (IL-6) and incident type-2 diabetes
among people in two large HIV treatment strategy trials – the SMART and
ESPRIT studies. The study participants were taking continuous ART without any adjunct
therapy. Higher baseline hsCRP and IL-6 were associated with diagnosis with
type-2 diabetes during follow-up.
markers provide independent information for predicting the development of
diabetes,” comment the authors. “Experimental studies aimed at reducing
inflammation are needed to establish a causal relationship.”
treatment and care mean that many people with HIV now have an excellent
life expectancy. However, HIV infection – even in the context of effective ART – is associated with a higher risk of
metabolic complications, including the development of type-2 diabetes. The
reasons for this are unclear, but possible causes include the side-effects of
some anti-HIV drugs and the inflammatory effects of HIV infection, which can persist
at low levels even in the context of ART.
Results of several
studies in the general population suggest that higher levels of hsCRP and IL-6
are associated with incident type-2 diabetes. But it is unclear if this is also
the case in people living with HIV.
therefore conducted a retrospective analysis of the relationship between
baseline hsCRP and IL-6 and incident type-2 diabetes in approximately 3700 people enrolled in the SMART and ESPRIT studies.
studies explored the safety and efficacy of CD4-guided structured interruptions
in ART (SMART) and the use of IL-2 adjunct therapy (ESPRIT). The present
analysis was restricted to people taking continuous ART who were not randomised
to receive IL-2.
Average CD4 count
at baseline was 523 cells/mm3 and participants were followed for an
average of 4.6 years (2.9 years in SMART and 6.8 years in ESPRIT). Type-2
diabetes was diagnosed in 137 people (3.5), a rate of 8.18 per 1000
The proportion of people with a CD4 count above 500 cells/mm3 and virologic
suppression remained unchanged during follow-up.
Median hsCRP and
IL-6 levels were significantly higher among people who developed type-2
diabetes compared to people who did not (hsCRP = 4.91 vs 3.29 μg/ml, p <
0.001; IL-6 = 3.45 vs 2.50 pg/ml, p < 0.001).
A doubling of baseline hsCRP levels increased the risk of
type-2 diabetes by approximately a fifth (HR = 1.22; 95% CI, 1.10-1.36, p <
0.001), whereas a doubling of baseline IL-6 increased the risk by almost a
third (HR = 1.29; 95% CI, 1.08-1.55, p = 0.005).
A number of traditional risk factors were also associated
with the diagnosis of diabetes. These included higher body mass index (p <
0.001), older age (p = 0.0.013), co-infection with hepatitis B or C virus (p =
0.03) and the use of lipid-lowering medication (p = 0.008).
The authors believe their findings offer “clues” as to why people living with HIV remain at increased risk of cardiovascular disease and other
chronic illness even when they are taking effective ART, and conclude, “our
findings support the hypothesis that low-grade systemic inflammation is an
underlying factor in the pathogenesis of type-2 diabetes.”