Evaluation of Serum Biochemical Parameters and Metabolism in Smokers: A Case Control Study

Smoking tobacco is a substantial risk factor for chronic obstructive pulmonary disease and cardiovascular diseases. For this reason, studies on smoking are mostly focused on the pulmonary and cardiovascular systems. Recently, an increase has been observed in the number of studies investigating the relationship between obesity and diabetes and smoking. We investigated the effects of smoking on other serum biochemical parameters and metabolism. This is a case-control study. The case and control groups were formed by clinical randomization by using the data obtained from the hospital information system and patient records, including age, gender, height, and weight. Smokers were identied as the case group, while non-smokers were identied as the control group. In the comparisons of rates Chi-square tests were used and in the comparisons of averages, independent sample t and MANCOVA tests were used.


Conclusions
We found that smoking has a negative effect on liver and bile functions, and vitamin D values are affected secondary to this negative effect.

Background
More than 5,000 chemical compounds have been identi ed in tobacco and tobacco smoke [1]. The most well-known of these substances is nicotine and identi ed with cigarettes. Nicotine is responsible for the addictive effect of smoking [2]. Smoking is one of the most important risk factors for chronic obstructive pulmonary disease [3,4]. Smoking is accepted to increase the risk of cardiovascular diseases [5,6].
Studies investigating the effects of smoking are mostly focused on the pulmonary and cardiovascular system. The number of studies on the effects of smoking on other systems such as the gastrointestinal system and urinary system than the pulmonary and cardiovascular system is not su cient to establish a consensus on the effects of cigaret on these systems. Recently, the number of studies investigating the relationship between smoking and obesity and diabetes has been observed to be increased [7,8]. We investigated the effects of smoking on several serum biochemical parameters and metabolism.

Study Design
This was designed to be a case-control study.

Population selection
The case and control groups were formed by clinical randomization by using the data obtained from the hospital information system and patient records, including age, gender, height and weight. The case group included 30 individuals with smoking habit and a control group consisted of non-smokers, matching with the case group in terms of number, gender, age and body mass index (BMI). Patients with any known disease and those using medications were not included in the study. Laboratory data of individuals who met the inclusion criteria among patients who admitted to the family medicine outpatient clinic during the last three-months were evaluated for analysis.

Laboratory testing
The blood samples of the participants were collected at the time of admission. A total of 19 parameters, including creatinine, urea, AST, ALT, GGT, sodium, potassium, albumin, cholesterol, triglyceride, HDL-C, LDL-C, HbA1C, glucose, insulin, vitamin D, vitamin B12, TSH, and free T4 were measured simultaneously for the analysis.

Statistical analysis
All statistical analyzes were performed by using IBM SPSS software (V25). A value of P <.05 was considered statistically signi cant. Categorical data were expressed by numbers and percentages. In the comparison of categorical variables chi-square test was used. Numerical data were expressed by mean values. In the comparison of the means independent sample t and MANCOVA tests were used. The compliance of the variances with normal distribution was tested by using box's and levene's tests.

Results
There was no difference between the case and control groups in terms of gender and BMI. However, the rate of alcohol use was lower in the case group compared to the control group. The mean age was higher in the case group compared to the control group (Table 1). According to independent sample t test analysis between smokers and non-smokers; were found signi cant differences in terms of serum AST, ALT, GGT, LDL-C, vitamin D, vitamin B12 and TSH levels. We found that AST, ALT GGT, and LDL-C levels were higher in the case group, whereas vitamin D, vitamin B12 and TSH levels were higher in the control group (Table 2). 2.36, P = .013). When the covariance factors were considered, we found that the difference between the two groups continued for AST, ALT, GGT, vitamin D, vitamin B12, and TSH, whereas the difference did not continued for LDL-C (Table 3). There was no signi cant difference between the case group and the control group in terms of glycemic parameters. However, HOMA-IR values were higher in the case group while HbA1C values were higher in the control group (Table 3).

Discussion
The fact that the alcohol use rate was lower and the average age was higher in the case group in comparison to the control group, indicates that randomization was not performed very well. However, this limitation has been minimized by one-way MANCOVA analyzes performed by considering covariance factors such as age, gender, BMI and alcohol use.
In our study, the higher values of serum AST, ALT, and GGT observed in the case group indicates that smoking affects liver and bile functions, negatively. In the literature there are studies that support our results. In a study conducted on males, GGT was higher in smokers in comparison to non-smokers [9]. It has also been suggested that smoking causes cellular damage by causing oxidative stress and ultrastructural changes on hepatocytes [10].
In our study, the lower serum vitamin D values in the case group compared to the control group may be caused by a defect in the vitamin D synthesis in the liver and / or an absorption disorder. Cholecalciferol synthesized in the epidermis or taken with diet turns into 25-hydroxycholecalcidiol in the liver and then to 1,25-hydroxycholecalcitriol as the active form in the kidney [11]. The 25-hydroxycholecalcididol transformation that takes place in the liver may be impaired due to the negative effects of smoking on hepatocytes. In addition, absorption of Vitamin D, a fat-soluble molecule, may be impaired due to the negative effects of smoking on the biliary system. In the literature, there are a few studies supporting our results, related to vitamin D in our study. However, the reasons for vitamin D de ciency in smokers have not been fully clari ed in these studies [12].
We found that, serum vitamin B12 values were lower in the case group compared to the control group.
These our results are in line with the knowledge in the literature. There are studies suggesting that smoking, which is a source of free radicals, causes serum vitamin B12 levels to decrease [13][14][15]. The use of tobacco causes the serum cyanide level to increase due to the cyanide it contains. It has been shown that high cyanide levels increase the excretion of thiocyanate from the kidneys, which is associated with a decrease in serum vitamin B12 level [16].
We found that serum TSH levels were lower in the case group compared to the control group. In the literature, it has been reported that the effects of smoking on thyroid tissue are complex, while smoking generally increases susceptibility to hypertroidism [17,18]. This relationship between smoking and thyroid functions may be due to vitamin B12 de ciency seen in smokers. Although there is a widespread opinion in the literature that vitamin B12 de ciency and increased levels of homocysteine increase susceptibility to hypothyroidism and autoimmune thyroid diseases, studies on animals suggest contradictory evidence [19][20][21]. In addition, S adenosyl methionine, a product of the homocysteine methionine cycle with additive vitamin B12 cofactor stimulates TRH and therefore TSH release and TSH receptor interaction [22].
In our study, we found no difference in kidney function, between smokers and non-smokers. In the literature, it has been reported that kidney functions are affected by smoking due to the increase in nicotine-induced adrenergic activity [23].
In our study, no signi cant difference was found between smokers and non-smokers in terms of serum glycemic index and lipid pro le. However, HOMA-IR values were higher in the case group while HbA1C values were higher in the control group. HOMA-IR values show the momentary state, while HbA1C shows the last three-month period. These ndings indicate that there was a predisposition to hypoglycaemia in the smoker group in the past. In a study conducted on obese people, HOMA-IR was found to be higher in smokers compared to non-smokers, but there was no signi cant difference in serum glucose, insulin, total cholesterol, triglyceride, HDL-C, and LDL-C levels [24]. Nicotine causes hyperglycemia by increasing gluconeogenesis by stimulating catecholamine-mediated glucagon release from the adrenergic medulla [8]. It is plausible that the relationship between smoking and insulin resistance, which is frequently emphasized in the literature, may be a result rather than a cause. Given the assumption that hyperinsullinemia-induced hypoglycaemia episodes seen at the onset of type 2 diabetes can be prevented by increasing gluconeogenesis, nicotine may be preferred due to an avoidance behavior.

Conclusions
As a result, we suggest that smoking has a negative effect on liver and bile functions, and vitamin D values are affected secondary to this negative effect. In addition, the relationship between smoking and thyroid functions may be due to vitamin B12 de ciency seen in smokers.