Serum levels of uncoupling proteins in patients with differential insulin resistance: A community-based cohort study

Abstract

The uncoupling protein (UCP) belongs to a family of energy-dissipating proteins in mitochondria. Increasing evidences have indicated that UCPs have immense impact on glucose homeostasis and are key proteins in metabolic syndrome. For applying the findings to clinical practice, we designed a study to explore the association between serum UCPs 1-3 and insulin resistance. This investigation prospectively recorded demographical parameter and collected blood samples of 1071 participants from 4 districts in Northeastern Taiwan during the period from August 2013 to July 2014. Propensity score matching by age and sex in patients with top and bottom third homeostasis model assessment of insulin resistance (HOMA-IR) levels was performed, and 326 subjects were enrolled for further studies. The mean age of the patients was 59.4 years and the majority of them (65.5%) were females. The prevalence of metabolic syndrome was 35.5%. Our results demonstrated that serum UCPs 1-3 were significantly associated with differences in HOMA-IR levels. Multiple logistic regression analysis indicated that low UCP 1 and features of metabolic syndrome, namely hypertension, diabetes, body mass index, and high-density lipoprotein, were independent determinants for high HOMA-IR levels. We thus determined that low serum UCP 1 is a predictor for high resistance to insulin.

Figure 1

Flow chart of study enrollment. From August 2013 to January 2014, a total of 1071 subjects aged 30 years and older were enrolled in the WARG cohort study. The subjects were divided into 3 groups according to the HOMA-IR level. After matching by age and sex in patients with the top and bottom third HOMA-IR levels, 326 of the 1071 subjects were identified and further classified into 2 groups: low HOMA-IR (n = 159) and high HOMA-IR (n = 167), according to the deviation of their HOMA-IR levels from the mean value (2.1). The expressions of serum UCP 1–3 of the 326 participants were further determined by the enzyme-linked immunosorbent assay. HOMA-IR = homeostasis model assessment of insulin resistance, UCP = uncoupling protein, WARG = Wanli, Anle, Ruifang, and Gongliao.

Figure 2

The correlation between serum UCP 1 and the features associated with metabolic syndromes. The overall trend of correlation between serum UCP 1 and features of metabolic syndrome, including (A) BMI, (B) fasting sugar, (C) MAP, (D) HDL, (E) LDL, and (F) TG displayed differences between low- and high-HOMA-IR patients. BMI = body mass index, HDL = high-density liproprotein, HOMA-IR = homeostasis model assessment of insulin resistance, LDL = low-density liproprotein, MAP = mean artery pressure, UCP = uncoupling protein.