Plasma heme oxygenase-1 concentration in relation to impaired glucose regulation in a non-diabetic Chinese population

Abstract

Background: Our previous study has recently shown that plasma heme oxygenase-1 (HO-1), a stress-responsive protein, is elevated in individuals with type 2 diabetes. The current study aimed to examine the association between plasma HO-1 concentration and impaired glucose regulation (IGR) in non-diabetic individuals.

Methods: We conducted a case-control study including a total of 865 subjects (262 IGR individuals and 603 healthy controls) in a Chinese population. Basic characteristics were collected by questionnaire and standardized anthropometric measurements. Plasma HO-1 concentration was determined by ELISA.

Results: Plasma HO-1 concentration was significantly increased in IGR individuals compared with healthy controls (1.34 (0.81-2.29) ng/ml vs 0.98 (0.56-1.55) ng/ml, P<0.001). After adjustment for age, sex, and BMI, the ORs for IGR in the highest quartile of plasma HO-1 concentrations, compared with the lowest, was 3.42 (95% CI 2.11-5.54; P for trend <0.001). The trend remained significant even after additional adjustment for smoking, alcohol drinking, hypertension, family history of diabetes, lipid profiles and C-reactive protein. In the receiver-operating characteristic curve analysis, addition of plasma HO-1 concentration to a model with known risk factors yielded significantly improved discriminative value for IGR (area under the curves 0.75 (95% CI 0.71-0.78) vs. 0.72 (95% CI 0.69-0.76); P for difference = 0.026).

Conclusions: Elevated plasma HO-1 concentration is significantly associated with increased ORs for IGR. However, its clinical utility should be validated in further studies, especially in prospective cohort studies.

Figure 1. Plasma HO-1 concentrations in IGR individuals and controls.

Plasma HO-1 concentration was significantly increased in individuals with IGR compared with controls (1.34 (0.81–2.29) ng/ml vs 0.98 (0.56–1.55) ng/ml, respectively; P<0.001).

Figure 2. ROC curves and corresponding AUCs for IGR using plasma HO-1 levels or HO-1 categories.

The AUCs for plasma HO-1 levels and HO-1 categories were 0.64 (0.60–0.68) and 0.62 (0.58–0.66), respectively; P = 0.0006 for the difference of the AUCs. Plasma HO-1 concentrations were categorized in quartiles according to the healthy control group as follows: category 1, <0.56 ng/ml; category 2, 0.56–0.98 ng/ml, category 3, 0.98–1.55 ng/ml and category 4, ≥1.55 ng/ml.

Figure 3. ROC curves and corresponding AUCs for IGR using models without or with plasma HO-1 levels.

The AUC in a Model A, comprising age, sex, BMI, alcohol consumption, smoking, hypertention and family history of diabetes, was 0.72 (95% CI, 0.69–0.76) and that in Model B (Model A plus plasma HO-1 levels) was 0.75 (95% CI, 0.71–0.78); P = 0.026 for the difference of the AUCs.