The Role of Pro-Inflammatory Chemokines CCL-1, 2, 4, and 5 in the Etiopathogenesis of Type 2 Diabetes Mellitus in Subjects from the Asir Region of Saudi Arabia: Correlation with Different Degrees of Obesity

Abstract

Background: Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in developing nations. The high prevalence of obesity and related diabetes cases are attributed to rapid economic progress, physical inactivity, the consumption of high-calorie foods, and changing lifestyles.

Objectives: We investigated the roles of pro-inflammatory chemokines CCL1, 2, 4, and 5 in T2DM with varying levels of obesity in the Asir region of Saudi Arabia.

Materials and methods: In total, 170 confirmed T2DM subjects and a normal control group were enrolled. Demographic data, serum levels of CCL-1, 2, 4, and 5, and biochemical indices were assessed in the subjects and control groups by standard procedures.

Results: T2DM subjects were divided into four groups: A (normal body weight), B (overweight), C (obese), and D (highly obese). We observed that male and female control subjects had similar mean serum concentrations of pro-inflammatory chemokines CCL-1, 2, 4, and 5. T2DM subjects in all the four groups showed significantly higher levels of all the four chemokines compared to the controls, regardless of gender. In T2DM subjects with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL-1, 2, and 4 in T2DM subjects with increasing BMI. Serum CCL5 levels increased significantly in all T2DM subject groups. The increase in CCL5 was more predominant in normal-weight people, compared to overweight and obese T2DM subjects.

Conclusions: Male and female control subjects had similar serum levels of pro-inflammatory chemokines CCL-1, 2, 4, and 5. The progressive rise in blood concentrations of three pro-inflammatory chemokines CCL-1, 2, and 4 in T2DM subjects with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM subject groups. The selective and more pronounced increase in CCL5 in the T2DM group with normal BMI, compared to subjects with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 underexpression in overweight and obese T2DM subjects is due to some unexplained counterbalancing processes.

Keywords: CCL1; CCL2; CCL4; CCL5; obesity; pro-inflammatory chemokines; type 2 diabetes mellitus.

Figure 1

Map showing different provinces of Saudi Arabia. The study areas (Asir region) is encircled in red.

Figure 2

Histogram showing the distribution of age between controls (green) and T2DM subjects (red) across two genders.

Figure 3

Bar plot displaying the mean values of WHR and BMI across the T2DM subjects and control group. T2DM subjects in Group C had significantly higher BMI compared to Groups A and B with p < 0.01, whereas Group D subjects had very significantly increased BMI versus Groups A and B with p < 0.001, and also significantly increased BMI versus Group C with p < 0.01 (Figure 3).

Figure 4

Box plot showing anthropometric indices, biochemical parameters, and chemokine levels of control and T2DM subjects; 0 in green represents controls and 1 in red represents T2DM subjects.

Figure 5

Error diagram of chemokine CCL5 levels in male controls and T2DM subjects.

Figure 6

Error diagram of chemokine CCL5 levels in female controls and T2DM subjects.

Figure 7

Correlation plot of different variables in control and T2DM subjects. *** represents highly significant, ** represents significant, and * is significant but close to 0.05.

Figure 8

Correlation plot of four chemokines in control and T2DM subjects. *** represents highly significant correlation.