Association of Tumor Necrosis Factor Alpha, Interleukin 6, and C-Reactive Protein with the Risk of Developing Type 2 Diabetes: A Retrospective Cohort Study of Rural Thais.

The linkage of obesity, inflammation, and type 2 diabetes mellitus (T2DM) has been extensively investigated for over a decade. However, the association between inflammatory biomarkers, including C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α), and T2DM is still inconsistent and limited. Thus, this study is aimed at elucidating the association between inflammatory marker levels and the risk of developing T2DM in many aspects. Among 296 subjects enrolled in 2013, 248 non-T2DM subjects who were completely reinvestigated in 2014 and 2015 were included in a 2-year retrospective analysis. Multivariate logistic regression was performed to evaluate the association of baseline inflammatory marker levels and variation with incidence of T2DM. After the 2-year follow-up, 18.6% of total subjects had developed T2DM. The risk of developing T2DM was significantly increased in subjects with a high level of baseline CRP (OR = 4.02, 95% CI: 1.77-9.12, P = 0.001), and a stronger impact was found with the combination of high CRP and IL-6 levels (OR = 5.11, 95% CI: 1.27-20.49, P = 0.021). One-year inflammatory marker variation analysis also revealed the significant association of elevated TNF-α and risk of developing T2DM (OR = 4.88, 95% CI: 1.01-23.49, P = 0.048). In conclusion, besides consideration of CRP levels alone, our findings suggested that IL-6 outstandingly plays a contributing role in T2DM progression and elevated TNF-α levels over time could be a potential predictor of T2DM.

Association of retinol binding protein 4 and transthyretin with triglyceride levels and insulin resistance in rural thais with high type 2 diabetes risk.

BACKGROUND: Retinol binding protein 4 (RBP4), a protein secreted by adipocytes and bound in plasma to transthyretin (TTR), has been associated with obesity, the early phase of insulin resistance, metabolic syndrome, and type 2 diabetes mellitus. The objective of this study was to elucidate the relationship between RBP4, TTR, triglyceride (TG) and type 2 diabetes risk in rural Thailand. METHODS: We measured the serum RBP4, TTR, glucose, triglyceride and insulin levels, and glucose tolerance of 167 volunteers from Sung Noen District, Nakhon Ratchasima Province, Thailand. Student's t-test, Pearson's correlation and logistic regression analysis were used to evaluate the relationships between RBP4, TTR and type 2 diabetes markers. RESULTS: RBP4 and TTR levels, as well as homeostatic model assessment of insulin resistance (HOMA-IR) values, were significantly elevated among subjects with high triglyceride levels (p < 0.01, p < 0.05, p < 0.05, respectively). Triglyceride levels correlated with RBP4 (r = 0.34, p < 0.001) and TTR (r = 0.26, p < 0.01) levels, as well as HOMA-IR values (r = 0.16, p < 0.05). After adjustment for age and gender, the risk of hypertriglyceridemia was 3.7 times greater (95% CI =1.42-9.73, p = 0.008) in the highest RBP4 tertile as compared to the lowest tertile. Similarly, the highest TTR and HOMA-IR tertiles had greater risk of hypertriglyceridemia at 3.5 (95% CI = 1.30-9.20, p = 0.01) and 3.6 (95% CI = 1.33-9.58, p = 0.01) times higher than the respective lowest tertiles. The correlation between TTR and blood glucose was statistically significant (r = 0.18, p < 0.05), but not found this relationship in RBP4. CONCLUSIONS: The associations of RBP4 and TTR with hypertriglyceridemia and insulin resistance may have important implications for the risk of heart disease and stroke.

Elevated C-reactive protein, interleukin 6, tumor necrosis factor alpha and glycemic load associated with type 2 diabetes mellitus in rural Thais: a cross-sectional study.

BACKGROUND: The elevated levels of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL6) are supposed to be associated with type 2 diabetes mellitus (T2DM). Frequent high glycemic load (GL) consumption, central obesity, and a lack of physical activity are considered to be T2DM risk factors. This study aimed to determine the difference of these inflammatory markers as well as GL in individuals with versus those without T2DM in rural Thais. METHODS: A total of 296 participants aged 35-66 living in Sung Noen District, Nakhon Ratchasima Province, Thailand, were recruited. Blood was collected to evaluate blood glucose levels, lipid profiles, and inflammatory markers. A Semi-food frequency questionnaire was utilized to assess GL followed by socioeconomic and anthropometric assessment. Statistical analysis was subsequently performed. RESULTS: Elevated CRP and IL6 levels were associated with increased risk of developing T2DM [OR (95% CI): 7.51 (2.11, 26.74) and 4.95 (1.28, 19.11)], respectively. There was a trend towards increased risk of T2DM with elevated TNF-α levels [OR (95% CI): 1.56 (0.39, 6.14)]. GL correlated significantly with fasting blood glucose (r = 0.289, P = 0.016), suggesting that it is involved in T2DM in this study group. CONCLUSION: In this study, CRP, IL6, and TNF-α associated with T2DM. Our findings suggested that these inflammatory markers, especially CRP, may initiate T2DM.

Risk factors for mortality in symptomatic hyperlactatemia among HIV-infected patients receiving antiretroviral therapy in a resource-limited setting.

OBJECTIVES: To determine the mortality rate and risk factors after experiencing symptomatic hyperlactatemia in HIV-infected patients receiving antiretroviral therapy (ART). METHODS: A retrospective cohort study was conducted among patients who were diagnosed with symptomatic hyperlactatemia (lactate >2.5mmol/l) between January 2004 and April 2006. All patients were followed until 3 months after the diagnosis. RESULTS: One hundred and twenty-five patients were included in the study. The mean+/-standard deviation (SD) age was 39.9+/-10.1 years and body weight was 58.2+/-16.9kg; 60.8% were male. Symptomatic hyperlactatemia in 114 (91.2%) was associated with receiving d4T, in five (4.0%) with d4T+ddI, in four (3.2%) with ZDV+ddI, and in two (1.6%) with ddI (d4T, stavudine; ddI, didanosine; ZDV, zidovudine). The median duration of ART was 13 months. Nine (7.2%) patients died. Patients who died had a higher mean lactate level (8.0 vs. 5.1mmol/l) and mean alanine aminotransferase (ALT; 164 vs. 48U/l) at the time of diagnosis when compared to those who survived (p<0.05). Patients who died had a lower mean weight than those who survived (48 vs. 59kg, p=0.008). By logistic regression, mortality was associated with patients whose body weight was <45kg (p=0.014, odds ratio (OR) 9.090, 95% confidence interval (CI) 1.575-52.632) and whose serum lactate was >10mmol/l (p=0.004, OR 20.372, 95% CI 2.610-159.001). CONCLUSIONS: The mortality rate of symptomatic hyperlactatemia among HIV-infected patients receiving ART is substantial. Almost all patients received d4T. Patients who have a low body weight and high serum lactate level are at a higher risk of mortality.

Options for a second-line antiretroviral regimen for HIV type 1-infected patients whose initial regimen of a fixed-dose combination of stavudine, lamivudine, and nevirapine fails.

BACKGROUND: A fixed-dose combination of stavudine, lamivudine, and nevirapine is extensively used as an antiretroviral regimen in developing countries because of its affordability. Virological failure with this regimen has become more common, and a second-line regimen needs to be prepared in the national program. METHODS: Genotypic resistance testing was conducted among human immunodeficiency virus type 1 (HIV-1)-infected patients who experienced treatment failure with their first antiretroviral regimen (a fixed-dose combination of stavudine, lamivudine, and nevirapine) during 2003-2005. Patterns of resistance mutations and options for a second-line regimen were studied. RESULTS: We studied 98 patients (mean age, 35.2 years), of whom, 63% were male. The median duration of antiretroviral therapy was 20 months. The median HIV-1 RNA load at the time of virological failure detection was 4.1 log copies/mL. The prevalences of patients with > or =1 major mutation conferring drug resistance to nucleoside reverse-transcriptase inhibitors and nonnucleoside reverse-transcriptase inhibitors were 95% and 92%, respectively. M184V was the most common nucleoside reverse-transcriptase inhibitor resistance mutation (observed in 89% of patients). Thymidine analogue mutations, K65R, and Q151M were observed in 37%, 6%, and 8% of patients, respectively. Patients with an HIV-1 RNA load of >4 log copies/mL at the time of treatment failure had higher prevalence of thymidine analogue mutations (P=.041), K65R (P=.031), and Q151M (P=.008) mutations. The second-line regimen was determined in a resource-limited setting where tenofovir and enfuvirtide are not available; the options were limited for 48% of patients. CONCLUSIONS: After experiencing treatment failure with a fixed-dose combination of stavudine, lamivudine, and nevirapine, almost all patients have lamivudine and nonnucleoside reverse-transcriptase inhibitor resistance. The options for a second-line regimen are limited for one-half of these patients. In resource-limited settings where availability of antiretroviral agents is limited, strategies for prevention of HIV-1 resistance are crucial. Early detection of virological failure may provide more options and better treatment outcomes.