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

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.

• Authors: Claude Béténé A Dooko, Stephane De Wit, Jacqueline Neuhaus, Adrian Palfreeman, Rosalie Pepe, James S Pankow, James D Neaton, INSIGHT SMART, ESPRIT Study Groups
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 67 Issue 5 Pg. 538-46 (Dec 15 2014) ISSN: 1944-7884 [Electronic] United States
• PMID: 25393940 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Retroviral Agents
• Interleukin-6
• C-Reactive Protein

Topics

• Adult
• Anti-Retroviral Agents (therapeutic use)
• C-Reactive Protein (analysis)
• Cohort Studies
• Diabetes Mellitus, Type 2 (epidemiology)
• Female
• HIV Infections (complications, drug therapy, pathology)
• Humans
• Interleukin-6 (blood)
• Longitudinal Studies
• Male
• Middle Aged
• Risk Assessment