Division of Endocrinology and Metabolism, Johns Hopkins University, Baltimore, Maryland, USA.
Diabetes Care. 2010 Oct;33(10):2244-9. doi: 10.2337/dc10-0633. Epub 2010 Jul 27.
To determine whether systemic inflammation after initiation of HIV-antiretroviral therapy (ART) is associated with the development of diabetes.
We conducted a nested case-control study, comparing 55 previously ART-naive individuals who developed diabetes 48 weeks after ART initiation (case subjects) with 55 individuals who did not develop diabetes during a comparable follow-up (control subjects), matched on baseline BMI and race/ethnicity. Stored plasma samples at treatment initiation (week 0) and 1 year later (week 48) were assayed for levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and the soluble receptors of tumor necrosis factor-α (sTNFR1 and sTNFR2).
Case subjects were older than control subjects (median age 41 vs. 37 years, P = 0.001), but the groups were otherwise comparable. Median levels for all markers, except hs-CRP, decreased from week 0 to week 48. Subjects with higher levels of hs-CRP, sTNFR1, and sTNFR2 at 48 weeks had an increased odds of subsequent diabetes, after adjustment for baseline marker level, age, BMI at week 48, CD4 count at week 48 (< vs. >200 cells/mm(3)), and indinavir use (all P(trend) ≤ 0.05). After further adjustment for week 48 glucose, effects were attenuated and only sTNFR1 remained significant (odds ratio, highest quartile vs. lowest 23.2 [95% CI 1.28-423], P = 0.03).
Inflammatory markers 48 weeks after ART initiation were associated with increased risk of diabetes. These findings suggest that systemic inflammation may contribute to diabetes pathogenesis among HIV-infected patients.
确定 HIV 抗逆转录病毒治疗（ART）起始后全身炎症是否与糖尿病的发生有关。
我们进行了一项嵌套病例对照研究，比较了 55 例在 ART 起始后 48 周发生糖尿病的初治患者（病例组）和 55 例在相当随访期间未发生糖尿病的患者（对照组），匹配了基线 BMI 和种族/民族。在治疗起始（第 0 周）和 1 年后（第 48 周）储存的血浆样本中测定高敏 C 反应蛋白（hs-CRP）、白细胞介素-6（IL-6）和肿瘤坏死因子-α的可溶性受体（sTNFR1 和 sTNFR2）水平。
病例组比对照组年龄更大（中位数年龄分别为 41 岁和 37 岁，P=0.001），但两组在其他方面无差异。除 hs-CRP 外，所有标志物的中位数水平从第 0 周降至第 48 周。在第 48 周时 hs-CRP、sTNFR1 和 sTNFR2 水平较高的患者，在调整了基线标志物水平、年龄、第 48 周 BMI、第 48 周 CD4 计数（<200 细胞/mm3 和>200 细胞/mm3）和使用沙奎那韦（所有 P（趋势）≤0.05）后，其随后发生糖尿病的可能性增加。在进一步调整第 48 周血糖后，作用减弱，只有 sTNFR1 仍具有显著性（最高四分位数与最低四分位的比值，最高四分位与最低四分位的比值 23.2[95%CI 1.28-423]，P=0.03）。
ART 起始后 48 周时的炎症标志物与糖尿病风险增加相关。这些发现提示全身炎症可能在 HIV 感染患者的糖尿病发病机制中起作用。
