Association of C-reactive protein Levels with Fasting and Postload Glucose Levels According to Glucose Tolerance Status

Background and Aims

Several studies show that high serum C-reactive protein (CRP) levels are associated with an increased risk of diabetes, data that strongly supports a possible role for inflammation in diabetogenesis. The aim of this study was to determine whether elevated CRP levels are associated with fasting plasma glucose (FPG) and/or postload glucose levels according to the glucose tolerance status.

Methods

A total of 169 healthy males and non-pregnant females aged 18–65 years were enrolled in a population-based cross-sectional study. Individuals were allocated into groups with a new diagnosis of normal glucose tolerance (NGT) (n = 82), impaired fasting glucose (IFG) (n = 54), and impaired glucose tolerance (IGT) (n = 33). Elevated CRP was defined by CRP levels >3.0 and <10.0 mg/L, IFG by FPG ≥100 and <126 mg/dL, and IGT by plasma glucose concentration 2 h postload ≥140 and <200 mg/dL. A multiple regression linear analysis adjusted by body mass index, waist circumference, and lipid profile was performed to evaluate the association between CRP levels (independent variable) with FPG and 2 h postload glucose levels (dependent variables).

Results

Multivariate linear regression analysis showed a significant association between hsCRP levels with FPG (β = 0.536; 95% CI 1.03–5.1, p = 0.005) and 2 h postload glucose (β = 0.209; 95% CI 1.31–2.97, p = 0.01) in the IGT group, but not with FPG (β = 0.147; 95% CI 0.55–2.0, p = 0.25) and 2 h postload glucose (β = 0.151; 95% CI 0.83–3.2, p = 0.24) in the IFG group.

Conclusions

Elevated CRP levels are associated with FPG and 2 h postload glucose in the individuals with IGT, but not in subjects with IFG or NGT.

Introduction

The low-grade chronic inflammatory syndrome characterized by mild elevation in the circulating levels of the named acute phase proteins is related with obesity and high glucose levels, suggesting that activation of the inflammatory response plays an important role in the pathogenesis of type 2 diabetes (T2D) 1, 2, 3, 4. Common underlying mechanisms involved in the link between inflammation and glucose metabolic disruption includes the activation of nuclear factor-κB and JUN N-terminal kinase, pathways that lead to the recruitment of cells of the immune system in adipose tissue 5, 6. Activation of the innate immune cells induces the expression of pro-inflammatory cytokines in the liver and adipose tissue, cytokines that may also be transported through the circulation to affect more distant tissues (7). Elevated levels of pro-inflammatory cytokines promote the synthesis and release of acute phase proteins by the liver, promoting the development of insulin resistance 1, 7, supporting the hypothesis that obesity is associated with inflammation and that the pathogenesis of T2D can be viewed as an auto-inflammatory disease (8).

Cross-sectional studies consistently show the association between circulating levels of acute-phase proteins such as the C-reactive protein (CRP) with T2D (9), glucose intolerance 10, 11, fasting hyperinsulinemia (12), insulin resistance 11, 13 and components of metabolic syndrome (MetS) (14), suggesting that inflammatory processes may be of particular importance in the pathogenesis of glucose metabolic disorders (15).

Prospective studies show that high baseline level of serum CRP is associated with an increased risk of diabetes 16, 17, 18, 19, 20, 21, 22, 23, data that strongly support a possible role for inflammation in diabetogenesis.

Clinical studies using anti-inflammatory drugs to treat T2D or prediabetes are scarce 24, 25, 26, 27, 28 and show that anti-inflammatory treatment improves β-cell secretory function and insulin sensitivity, lowering the blood glucose levels. These findings support a causative role for inflammation in the pathogenesis of T2D. Furthermore, studies conducted in obese prediabetic subjects 27, 28 show that salicylates reduce the glycemia (27) glucose-lowering effect that appears to be due to effects on insulin concentration rather than in the improvement of insulin action (28).

Among all these studies, the relationship between low-chronic inflammation and impaired glucose tolerance (IGT) has been well established 18, 29, whereas the relationship between chronic systemic inflammation and isolated impaired fasting glucose (IFG) has not been established with certainty 11, 12 with reports showing controversial results 25, 30, 31. In this regard, to the best of our knowledge, the relationship between CRP levels with the fasting plasma glucose (FPG) and postload glucose in the states of glucose tolerance status has not been previously reported. Thus, the objective of this study was to determine whether elevated CRP levels are associated with FPG and/or postload glucose levels according to the glucose tolerance status.