Role of secreted frizzled-related protein 4 in prediabetes and type 2 diabetes: a cross sectional study

Abstract

Background: Type 2 diabetes (T2D) has become an epidemic. Delays in diagnosis and as a consequent late treatment has resulted in high prevalence of complications and mortality. Secreted frizzled-related protein 4 (SFRP4), has been recently identified as a potential early biomarker of T2D related to obesity, due to its association with low grade inflammation in adipose tissue and impaired glucose metabolism. We aimed to evaluate the role of SFRP4 in prediabetes and T2D in a Mexican population.

Methods: This was a cross-sectional study that included 80 subjects with T2D, 50 subjects with prediabetes and 50 healthy individuals. Fasting SFRP4 and insulin concentrations were measured by ELISA. Human serum IL-10, IL-6, IL-1β and IL-8 levels were quantified by flow cytometry. Genotyping was performed by TaqMan® probes.

Results: Prediabetes and T2D patients had significantly higher SFRP4 levels than controls (P < 0.05). In turn, prediabetes subjects had higher SFRP4 concentrations than control subjects (P < 0.05). Additionally, the prediabetes and T2D groups had higher concentrations of proinflammatory molecules such as IL-6, IL-1β and IL-8, and lower concentrations of IL-10, an anti-inflammatory cytokine, than controls (P < 0.001). The serum SFRP4 concentrations were positively correlated with parameters that are elevated in prediabetes and T2D states, such as, HbA1c and homeostasis model assessment insulin resistance (HOMA-IR), (r = 0.168 and 0.248, respectively, P < 0.05). Also, serum SFRP4 concentrations were positively correlated with concentrations of pro-inflammatory molecules (CRP, IL-6, IL-1β and IL-8) and negatively correlated with the anti-inflammatory molecule IL-10, even after adjusting for body mass index and age (P < 0.001). The genetic variant rs4720265 was correlated with low HDL concentrations in T2D (P < 0.05).

Conclusions: SFRP4 correlates positively with the stage of prediabetes, suggesting that it may be an early biomarker to predict the risk of developing diabetes in people with high serum concentrations of SFRP4, although further longitudinal studies are required.

Keywords: Biomarker; Prediabetes; SFRP4; insulin resistance; Type 2 diabetes.

Fig. 1

Serum SFRP4 levels in the three study groups. Columns represent the mean with standard deviation. CTRL, control group; PRE, Prediabetes group; T2D, type 2 diabetes group. The Kruskal-Wallis test was performed

Fig. 2

Spearman correlations between SFRP4 and anthropometric and biochemical parameters adjusted by BMI, age and sex. P < 0.05 was considered significant. Abbreviations: BMI, body mass index; WC, waist circumference; WHR, waist hip ratio; HbA1c, glycated hemoglobin; HOMA-IR, homeostasis model assessment insulin resistance. Crosses represent control group; white squares represent prediabetes group and black circles represent T2D group

Fig. 3

Spearman correlations between SFRP4 and pro-inflammatory molecules. P < 0.05 was considered significant Correlations were adjusted by BMI, age and sex. Abbreviations: CPR, C-protein reactive; IL-6, interleukin 6; IL-8, interleukin 8; IL-1b, interleukin 1 beta; IL-10, interleukin 10. Crosses represent control group; white squares represent prediabetes group and black circles represent T2D group