3.1. The concentrations of IL-6 and glucagon in the obesity and the diabetes groups
Statistically higher levels of IL-6 were observed in both obese (p = 0.022) and diabetic (p < 0.000) groups compared to the control group. In turn, higher levels of glucagon were observed in the diabetic group compared to the control (p < 0.000) and obese (p = 0.001) groups. The obtained results are presented in Table 3. Concentrations of glucose, insulin, CRP, and selected metals (zinc, copper, cadmium) between these groups have already been presented in previous studies (28,31).
Table 3
Concentrations of IL-6 and glucagon in the control, obese and diabetic groups.
Parameter | Control group (N = 50) | Obese group (N = 45) | Diabetic group (N = 23) |
IL-6 [pg/mL] | {7.37; 10.61; 34.30} | {6.22; 6.62; 9.53}* | {5.91; 6.21; 7.17}* |
Glucagon [pg/mL] | {58.41; 86.54; 120.72} | {44.35; 77.86; 112.20} | {130.80; 173.18; 219.27}*,** |
Values shown as {1st quartile; median; 3rd quartile}.
* p < 0.05 – compared to control group; ** p < 0.05 – compared to obese group
3.2. The influence of the rs1800795 polymorphism in IL6 gene on the concentrations of the selected parameters associated with glucose metabolism and concentrations of selected metals
There were no statistically significant differences in the genotypic distribution (rs1800795, IL6 gene) between the control group, the group of obese patients, and the group of diabetic patients. The results are shown in Table 4.
Table 4
The genotypic distribution of the rs1800795 polymorphism (IL6) in the control, obese and diabetic groups.
Genotype | Control group | Obese group | Diabetic group |
G/G N = 36 (30.51%) | N = 18 (50.00%) | N = 15 (41.67%) | N = 3 (8.33%) |
G/C N = 50 (42.37%) | N = 18 (36.00%) | N = 23 (46.00%) | N = 9 (18.00%) |
C/C N = 32 (27.12%) | N = 14 (43.75%) | N = 7 (21.88%) | N = 11 (34.37%) |
A statistically higher insulin concentration was demonstrated in the obese group with the G/G genotype (rs1800795, IL6 gene) compared to the control group with the same genotype (p = 0.026) (Table 5). It was similar in the group of patients with the G/C genotype, in which higher insulin concentrations were also shown in the obese group (p = 0.004) and diabetic group (p = 0.007) compared to the control group. In turn, in the group of patients with the C/C genotype, higher insulin concentration was demonstrated in the diabetic group compared to the control group (p = 0.008). However, no significant differences in glucagon concentrations were observed.
A statistically lower concentration of IL-6 was observed in obese people with the G/G genotype compared to the control group with the same genotype (p = 0.014). A lower concentration of IL-6 was also shown in the diabetic group with the C/C genotype compared to the control group (p = 0.009) and the obese group (p = 0.044) with the same genotype.
As far as glucose is concerned, the following changes were observed: higher concentration in the diabetic group with the G/G genotype compared to the control group with the same genotype (p = 0.005); higher concentration in the diabetic group with the G/C genotype compared to the control group (p < 0.000) and the obese group (p = 0.003) with the same genotype; higher concentration in the diabetic group with the C/C genotype compared to the control group with the same genotype (p < 0.000).
Higher CRP concentrations were observed in obese patients with the G/G genotype compared to the control group with the same genotype (p = 0.003). Similarly, higher concentrations of this parameter were noticed in obese patients (p = 0.006) and diabetic patients (p = 0.001) with the G/C genotype compared to the control group with the same genotype. Higher CRP concentrations were also observed in obese patients with the C/C genotype compared to patients from the control group with the same genotype (p = 0.008).
Finally, higher copper concentrations were demonstrated in diabetics with the G/C genotype (p = 0.002) and the C/C genotype (p = 0.043) compared to the control groups with the corresponding genotypes. As in the case of the rs3842729 polymorphism, no significant differences in zinc and cadmium concentrations were observed. All of the above results are shown in Table 5.
Table 5
Concentrations of the selected parameters associated with glucose metabolism in terms of rs1800795 (IL6).
Parameter | Control group (N = 50) | Obese group (N = 45) | Diabetic group (N = 23) |
G/G (N = 18) | G/C (N = 18) | C/C (N = 14) | G/G (N = 15) | G/C (N = 23) | C/C (N = 7) | G/G (N = 3) | G/C (N = 9) | C/C (N = 11) |
Insulin [mU/L] | 6.40; 7.90; 9.00 | 4.20; 6.30; 8.20 | 4.50; 5.20; 6.90 | 7.90; 13.60; 14.80* | 9.65; 14.55; 17.75*** | 7.40; 10.25; 19.30 | 4.09; 13.92; 41.70 | 10.65; 17.39; 23.17*** | 8.13; 9.91; 20.45$$ |
Glucagon [pg/mL] | 59.27; 88.35; 125.93 | 58.41; 86.54; 97.54 | 39.20; 74.36; 131.80 | 44.35; 103.36; 112.20 | 46.22; 67.35; 106.85 | - | 82.88; 170.00; 299.41 | 130.80; 173.18; 195.75 | 140.13; 181.69; 221.05 |
IL-6 [pg/mL] | 8.85; 12.02; 23.68 | 6.07; 8.90; 76.92 | 7.46; 9.91; 20.31 | 6.10; 6.40; 8.78* | 6.22; 6.87; 13.52 | 7.06; 8.74; 9.90 | 6.24; 7.17; 7.18 | 5.84; 6.01; 8.94 | 5.92; 6.08; 6.29$$,$$$ |
Glucose [mmol/L] | 4.56; 4.72; 4.83 | 4.44; 4.81; 5.00 | 4.44; 4.72; 5.06 | 4.72; 5.17; 5.50 | 4.92; 5.17; 5.53 | 5.03; 5.36; 6.25 | 6.04; 9.20; 11.10* | 6.60; 6.80; 9.50***,$ | 6.30; 8.25; 8.50$$ |
CRP [mg/L] | 0.20; 0.47; 0.80 | 0.37; 0.89; 1.15 | 0.32; 0.61; 0.91 | 1.11; 1.22; 1.48* | 0.97; 1.34; 3.19*** | 1.80; 4.52; 6.93$$ | 0.62; 1.33; 14.24 | 1.38; 2.79; 5.41*** | 0.69; 1.04; 2.25 |
Cu [µg/L] | 960.21; 1012.89; 1257.32 | 853.30; 988.99; 1055.65 | 912.33; 994.74; 1059.29 | 889.84; 1001.59; 1114.89 | 991.47; 1075.33; 1167.87 | 974.55; 1148.39; 1321.91 | 1011.00; 1206.00; 1490.00 | 1121.00; 1248.00; 1325.00*** | 1016.00; 1082.00; 1221.00$$ |
Zn [µg/L] | 940.35 ± 130.09 | 969.25 ± 126.96 | 987.86 ± 151.71 | 943.94 ± 118.78 | 985.36 ± 92.38 | 880.19 ± 133.20 | 802.00 ± 47.29 | 902.67 ± 77.86 | 899.36 ± 102.83 |
Cd [mg/g Hg] | 1.07; 2.46; 3.39 | 1.63; 1.87; 3.56 | 1.62; 2.43; 3.64 | 1.54; 2.91; 6.04 | 1.78; 4.22; 5.50 | 2.07; 4.49; 11.13 | 1.69; 3.09; 5.15 | 2.52; 3.59; 7.82 | 1.79; 3.83; 5.04 |
Values shown as: mean value ± standard deviation or {1st quartile; median; 3rd quartile}.
* p < 0.05 – compared to control group with G/G genotype; ** p < 0.05 – compared to obese group with G/G genotype; *** p < 0.05 – compared to control group with G/C genotype; $ p < 0.05 – compared to obese group with G/C genotype; $$ p < 0.05 – compared to control group with C/C genotype; $$$ p < 0.05 – compared to obese group with C/C genotype.
3.3. The influence of the rs3842729 polymorphism in INS gene on the concentrations of the selected parameters associated with glucose metabolism and concentrations of selected metals
There was no statistically significant difference in the genotypic distribution (rs3842729, INS gene) between the control group, the group of obese patients, and the group of diabetic patients. The results are shown in Table 6.
Table 6
The genotypic distribution of the rs3842729 polymorphism (INS) in the control, obese and diabetic groups.
Genotype | Control group | Obese group | Diabetic group |
A/G N = 61 (51.69%) | N = 23 (37.71%) | N = 29 (47.54%) | N = 9 (14.75%) |
G/G N = 57 (48.31%) | N = 27 (47.37%) | N = 16 (28.07%) | N = 14 (24.56%) |
A statistically lower IL-6 concentration was found in diabetic patients with the A/G genotype (p = 0.002) and the G/G genotype (p = 0.025) compared to the control group with corresponding genotypes (Fig. 1A).
Higher levels of glucagon were observed in the group of diabetics with the A/G genotype compared to the control group (p = 0.048) and obese group (p = 0.043) with the same genotype, and also in the group of diabetic patients with the G/G genotype (p = 0.005) compared to the control group with the same genotype. These results are shown in Fig. 1.
1 – control group; 2 – obese group; 3 – diabetic group
The asterisk marks a statistically significant difference compared with the control group with A/G genotype (p < 0.05). The circle marks a statistically significant difference compared with control group with G/G genotype (p < 0.05). The triangle marks statistically significant difference compared with the obese group with A/G genotype (p < 0.05).
Statistically higher levels of insulin were observed in obese patients with the G/G genotype (p = 0.003) compared to the control group with the same genotype. What is more, higher glucose concentrations were also shown in obese patients with the A/G genotype (p = 0.015) compared to the control group with the same genotype.
Higher CRP concentrations were observed in obese patients with the A/G genotype (p < 0.000) and diabetic patients with the A/G genotype (p = 0.030) compared to the control group with the same genotype. The situation was similar in the case of patients with the G/G genotype (p = 0.001 and p < 0.000, respectively).
No significant differences were observed for the concentrations of copper, zinc, and cadmium. All of the above results are shown in Table 7. The concentrations of insulin, glucose, and metals in the group of diabetic patients separated into genotypes (A/G and G/G) in terms of rs3842729 polymorphism in the INS gene were presented in an earlier publication (28).
Table 7
The concentrations of the selected parameters associated with glucose metabolism in terms of rs3842729 (INS).
Parameter | Control group (N = 50) | Obese group (N = 45) | Diabetic group (N = 23) |
A/G (N = 23) | G/G (N = 27) | A/G (N = 29) | G/G (N = 16) | A/G (N = 9) | G/G (N = 14) |
Insulin [mU/L] | 4.90; 7.00; 8.20 | 4.70; 6.80; 9.40 | 8.90; 10.95; 17.50* | 11.50; 14.60; 18.80*** | - | - |
Glucagon [pg/mL] | 60.90; 92.79; 120.72 | 50.92; 82.02; 119.29 | 44.35; 67.35; 112.20 | 47.60; 103.36; 106.85 | 130.80; 182.98; 221.05*,** | 140.13; 165.30; 195.75*** |
IL-6 [pg/mL] | 7.99; 10;83; 30.59 | 7.28; 10.56; 38.01 | 6.28; 6.73; 11.20 | 6.22; 6.46; 9.51 | 5.82; 5.96; 6.71* | 5.98; 6.36; 7.18*** |
Glucose [mmol/L] | 4.56; 4.78; 4.94 | 4.44; 4.64; 5.06 | 4.92; 5.17; 5.56* | 4.72; 5.17; 5.61 | - | - |
CRP [mg/L] | 0.37; 0.65; 0.93 | 0.19; 0.43; 0.94 | 0.99; 1.33; 2.82* | 1.14; 1.80; 5.26*** | 0.69; 1.33; 4.07* | 1.03; 1.72; 3.79*** |
Cu [µg/L] | 1018.49 ± 114.23 | 1007.20 ± 200.71 | 1084.97 ± 136.46 | 1072.88 ± 173.16 | - | - |
Zn [µg/L] | 924.60 ± 115.18 | 997.67 ± 141.60 | 953.02 ± 89.37 | 953.64 ± 145.95 | - | - |
Cd [mg/g Hg] | 1.49; 2.25; 3.51 | 1.46; 2.44; 3.60 | 1.59; 2.91; 4.92 | 2.73; 6.04; 14.52 | - | - |
Values shown as: mean value ± standard deviation or {1st quartile; median; 3rd quartile}.
* p < 0.05 – compared to control group with A/G genotype; ** p < 0.05 – compared to obese group with A/G genotype; *** p < 0.05 – compared to control group with G/G genotype.
3.4. The influence of IL6 and INS polymorphisms on the risk of occurrence of obesity or diabetes
This study also looked at the effects of several variables, including genotypic variability, on the development of obesity and T2D using logistic regression. In the context of the risk of obesity development, the following variables were significant: age and smoking. A one-year increase in age has been shown to be associated with an 8.70% (p < 0.000) increase in obesity risk. What is more, the odds of developing obesity are approximately 3.73-fold (p = 0.010) higher in cigarette smokers than in people who are not exposed to tobacco smoke.
In turn, in the context of the development of T2D, variables such as age, BMI values, and genotypic variability within the rs1800795 polymorphism have been found to be significant. It has been shown that patients with the G/G genotype are at approximately 4.72-fold (p = 0.037) lower odds to develop T2D compared to patients with other (G/C and C/C) genotypes. Moreover, it has been noticed that an increase in BMI by one unit increases the chance of developing T2D by approximately 67.20% (p < 0.000). As mentioned earlier, the risk also increases with age, but since elderly people predominated in the diabetic population in this study, the OR value may be overestimated, so it was not included. The described results are shown in Table 8 and Table 9.
Table 8
Relationship between the selected parameters and the risk of developing obesity.
SNP (gene) | Genotype | Obese group | Control group | p | OR | 95% CI OR |
rs1800795 (IL6) | G/G | 17 | 18 | 0.379 | 1.667 | 0.535–5.196 |
G/C | 26 | 18 | 0.094 | 2.556 | 0.853–7.655 |
| C/C | 14 | 14 | - | 1.000 | - |
rs3842729 (INS) | A/G | 32 | 23 | - | 1.000 | - |
G/G | 25 | 27 | 0.073 | 0.470 | 0.206–1.073 |
Other variables | Category | Obese group | Control group | p | OR | 95% CI OR |
Age [years] | - | - | - | < 0.000 | 1.087 | 1.045–1.131 |
Sex | Men | 27 | 21 | - | 1.000 | - |
Women | 30 | 29 | 0.270 | 0.634 | 0.281–1.426 |
Smoking status | Yes | 19 | 7 | 0.010 | 3.730 | 1.371–10.145 |
No | 38 | 43 | - | 1.000 | - |
OR – odds ratio; CI – confidence interval; statistical significance: p < 0.05 |
Table 9
Relationship between the selected parameters and the risk of developing type 2 diabetes.
SNP (gene) | Genotype | Diabetic group | Control group | p | OR | 95% CI OR |
rs1800795 (IL6) | G/G | 3 | 18 | 0.037 | 0.212 | 0.049–0.909 |
G/C | 9 | 18 | 0.431 | 0.636 | 0.207–1.959 |
| C/C | 11 | 14 | - | 1.000 | - |
rs3842729 (INS) | A/G | 9 | 23 | - | 1.000 | - |
G/G | 14 | 27 | 0.583 | 1.325 | 0.485–3.621 |
Other variables | Category | Diabetic group | Control group | p | OR | 95% CI OR |
BMI | - | - | - | < 0.000 | 1.672 | 1.305–2.143 |
Sex | Men | 6 | 21 | - | 1.000 | - |
Women | 17 | 29 | 0.195 | 2.052 | 0.692–6.084 |
Smoking status | Yes | 3 | 7 | 0.912 | 0.921 | 0.216–3.939 |
No | 20 | 43 | - | 1.000 | - |
OR – odds ratio; CI – confidence interval; statistical significance: p < 0.05 |