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. 2014 Dec 15;67(5):538-46.
doi: 10.1097/QAI.0000000000000354.

Interleukin-6, high sensitivity C-reactive protein, and the development of type 2 diabetes among HIV-positive patients taking antiretroviral therapy

Claude Béténé A Dooko  1 , Stephane De Wit, Jacqueline Neuhaus, Adrian Palfreeman, Rosalie Pepe, James S Pankow, James D Neaton; INSIGHT SMART; ESPRIT Study Groups
Affiliations

Interleukin-6, high sensitivity C-reactive protein, and the development of type 2 diabetes among HIV-positive patients taking antiretroviral therapy

Claude Béténé A Dooko et al. J Acquir Immune Defic Syndr. .

Abstract

Background: HIV infection is associated with increased levels of inflammatory markers. Inflammation is hypothesized to play a role in the development of type 2 diabetes. Data addressing this issue among HIV-positive participants are limited.

Methods: A cohort of 3695 participants without diabetes, taking antiretroviral therapy and with an average CD4⁺ count of 523 cells/mm³, were followed for an average of 4.6 years. Diabetes risk associated with baseline levels of high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) was assessed using Cox proportional hazards regression models. Analyses considered baseline levels of factors associated with diabetes risk and HIV-related measures.

Results: One hundred thirty-seven patients developed diabetes requiring drug treatment during follow-up (8.18 per 1000 person-years). Median levels of IL-6 and hsCRP were significantly higher among those who developed diabetes compared with those who did not: 3.45 versus 2.50 pg/mL for IL-6 and 4.91 versus 3.29 µg/mL for hsCRP (P < 0.001). Adjusted hazard ratios associated with a doubling of IL-6 and hsCRP were 1.29 (95% confidence interval: 1.08 to 1.55; P = 0.005) and 1.22 (95% confidence interval: 1.10 to 1.36; P < 0.001), respectively. Body mass index (P < 0.001), age (P = 0.013), coinfection with hepatitis B or C (P = 0.03), nonsmoking status (P = 0.034), and use of lipid-lowering treatment (P = 0.008) were also associated with an increased risk of diabetes.

Conclusions: These findings indicate that low-grade systemic inflammation is an underlying factor in the pathogenesis of diabetes.

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Figures

Figure 1
Figure 1
Boxplots of IL-6 and hsCRP according to the development of diabetes during follow-up. Percentiles of the IL-6 distribution for those with diabetes are: 10th percentile=1.14, 25th percentile=1.70, median = 2.35, 75th percentile=3.90, 90th percentile=6.30. For those without diabetes, the percentiles are: 10th percentile=0.80, 25th percentile=1.14, median = 1.80, 75th percentile=2.80, 90th percentile=4.46. Percentiles of the hsCRP distribution for those with diabetes are: 10th percentile=0.84, 25th percentile=1.63, median = 2.86, 75th percentile=5.12, 90th percentile=11.80. For those without diabetes, the percentiles are: 10th percentile=0.31, 25th percentile=0.67, median = 1.52, 75th percentile=3.52, 90th percentile=7.35.
Figure 2
Figure 2
Cumulative Percent Developing Diabetes by Quartile of IL-6. The number at risk in Quartiles 1, 2, 3 and 4 was 989, 1023, 962 and 991, respectively at baseline, 746, 841, 812 and 822 at year 2, 395, 570, 564 and 464 at year 4 and 194, 302, 282 and 211 at year 6. The p-value corresponding to a logrank test with 3 degrees of freedom that compares the incidence of diabetes by quartile is <0.001.
Figure 3
Figure 3
Cumulative Percent Developing Diabetes by Quartile of hsCRP. The number at risk in Quartiles 1, 2, 3 and 4 was 995, 987, 993, 990, respectively at baseline, 801, 822, 807 and 791 at year 2, 511, 522, 519 and 441 at year 4 and 268, 284, 246 and 191 at year 6. The p-value corresponding to a logrank test with 3 degrees of freedom that compares the incidence of diabetes by quartile is <0.001.
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