The human body contains few trace elements, but they have an important protective effect on human health and metabolism. As an indispensable trace element, Se mainly produces antioxidant defences and anti-inflammation and generates active thyroid hormones in the body in the form of selenoproteins(Reference Rayman1). The human body mainly absorbs Se in the form of a diet(Reference Shu, Wu and Yang2), and Se deficiency may harm human health(Reference Ferguson, Karunasinghe and Zhu3). Studies have shown that the intake of a certain amount of dietary Se has the potential to prevent the occurrence of bladder cancer, lung cancer and autoimmune thyroid disease and may also reduce the risk of diabetes(Reference Amaral, Cantor and Silverman4–Reference Kljai and Runje7).
Telomeres are composed of TTAGGG repeats at the ends of eukaryotic chromosomes, which shorten telomere length through mitosis in somatic cells(Reference Cheng, Carroll and Joglekar8). Telomere length has an impact on human longevity and health status and is considered a biomarker of ageing(Reference Huang, Liu and Lo9). A shorter telomere length is associated with an increased risk of age-related diseases, such as CVD, diabetes and dementia(Reference Fitzpatrick, Kronmal and Gardner10–Reference Yaffe, Lindquist and Kluse12). In addition, a healthy lifestyle (higher levels of physical activity or higher adherence to Mediterranean diet has been associated to longer TL(Reference Tucker13,Reference Nettleton, Diez-Roux and Jenny14) . Previous studies have reported an association between dietary Se intake and telomere length in middle-aged and elderly populations(Reference Shu, Wu and Yang2). However, the relationship between dietary Se intake and telomere length in the population with diabetes remains unknown. Therefore, we used the National Health and Nutrition Examination Survey database to examine the relationship between dietary Se and telomere length in patients with diabetes.
Methods
Study participants
The National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2002 comes from the Centers for Disease Control and Prevention’s survey, approved by the research ethics review board and downloaded from http://www.cdc.gov/nchs/nhanes/index.htm. Written informed consent was obtained from all the participants. A total of 1332 participants with diabetes constituted the study. We set the criteria for selecting participants. The participants were included if they had telomere length, after removing telomere length and Se mean standard exceeding three standard deviations (n 981). Then, the participants were included if they had telomere length and dietary Se, after removing telomere length and dietary Se mean standard exceeding three standard deviations (n 936) and no missing information regarding BMI, physical activity, education, cancer or malignancy and congestive heart failure (n 878). Therefore, a total of 878 participants with diabetes were included in the study, as shown in Fig. 1.
The flow chart of participants selection.
Dietary selenium intake assessment
All participants had their first face-to-face recall interview in a MEC private room in NHANES, asking for detailed information on the type of food intake 24 h prior to the interview (midnight to midnight) and estimating the composition of the ingested food. For each participant, dietary intake data were recorded using the NHANES computer-assisted dietary interview system, and all data were collected and transmitted through an automated system. Dietary data were processed using the University of Texas Food Intake Analysis System and the USA Department of Agriculture Survey Nutrition Database, coding individual foods and portion sizes to calculate the nutritional values of nutritional intake. It contains dietary Se and other dietary components(15,16) .
Telomere length assessment
Telomere length determination was performed in the laboratory of Dr. Elizabeth Blackburn, UC San Francisco, USA, selecting the blood sample of all participants in the NHANES database, using quantitative PCR methods to measure telomere length (T/S ratio) relative to standard reference DNA(17), as previously described in more detail(Reference Cawthon18,Reference Needham, Adler and Gregorich19) . The mean and standard deviation of the T/S ratio were calculated, and the interassay coefficient of variation was 6·5 %. Finally, the T/S ratio was converted to bp (formula: base pairs = 3274 + 2413 × (T/S)), which was calculated by comparing the telomere restriction fragment length analysed using Southern blot and the T/S ratio of DNA samples using human diploid fibroblast IMR90(Reference Needham, Rehkopf and Adler20). The methods and data conversion for telomere length determination have been described in detail on the official website (–https://wwwn.cdc.gov/Nchs/Nhanes/2001–2002/TELO_B.htm).
Covariates assessment
The covariates included age, sex, education, race, BMI (BMI; weight divided by height squared (kg/m2)), energy intake, hypertension, congestive heart failure, cancer or malignancy and physical activity. We categorised diabetes based on HbA1c level ≥ 6·5 %, fasting plasma glucose level ≥ 126 mg/dl or self-reported diabetes. We categorised ethnicity as non-Hispanic white, non-Hispanic black, Mexican American, other Hispanic or other races. Hypertension was categorised as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure average ≥ 90 mmHg or self-reported hypertension. Physical activity was categorised as no aerobic activity, low activity, moderate activity or high activity. According to the NHANES, no aerobic exercise was defined as predominately sitting during the day and infrequent activity; standing or walking all the time during the day and not requiring frequent extraction of items is called low physical activity; carrying lightweight items or frequent mountain climbing is defined as moderate activity and having to work at high loads or carrying heavy objects is defined as high physical activity(21). BMI was categorised as ≥ 30 kg/m2 or < 30 kg/m2. Age was categorised as > 45 years or ≤ 45 years.
Statistical analysis
First, the data were divided into two parts based on the male and female groups to find differences and general characteristics, using mean ± standard deviations or number and proportions to expression. Second, the data were used in a stratified analysis to determine the relationship between Se intake and telomere length in different age groups, sex, race, BMI, physical activity, education, hypertension, congestive heart failure, cancer or malignancy. We then constructed generalised linear models to assess the association between dietary Se intake and telomere length in patients with diabetes. The first model was adjusted for age and sex to estimate this association, while the second model was further adjusted for general demographic characteristics, including age, sex, ethnicity and education. The third model additionally controlled for physical activity, BMI, energy intake, hypertension, congestive heart failure and cancer or malignancy. Lastly, after controlling for sex, we constructed generalised linear models to assess the association between dietary Se intake and telomere length in patients with diabetes. All analyses were based on a two-sided significance level (P < 0·05). All analyses were performed using the statistical software packages R (http://www.R-project.org) and Empower stats (www.empowerstats.com, X&Y Solutions, Inc.).
Results
There were 878 participants with diabetes who were assessed for telomere length and dietary Se intake. The participants’ average age was 61·44 ± 13·82 years. The characteristics of the participants with diabetes in different sex groups are shown in Table 1, and those in different age groups are shown in Table 2.
Characteristics of the participants with diabetes in different sex groups
(Numbers and percentage, n 878)
Characteristics of the participants with diabetes in different age groups
(Numbers and percentages, n 878)
Subgroup analysis revealed a significant difference between Se intake and telomere length in women with diabetes (Table 3). The relationship between Se intake and telomere length in patients with diabetes in different models using a generalised linear model is shown in Table 4. In sex groups, we found 1 μg increase in dietary Se intake in female patients with diabetes, and then telomere length increased by 1·84 bp (β = 1·84 (95 % CI: 0·15, 3·53)) after controlling for age, education, race, physical activity, BMI, energy intake, hypertension, congestive heart failure, and cancer or malignancy.
Relationship between selenium intake and telomere length in patients with diabetes
(Numbers and 95 % confidence intervals, n 878)
Relationship between selenium and telomere length among diabetes in different models
(Numbers and 95 % confidence intervals)
Model 1 adjust for: sex; age.
Model 2 adjust for: sex; age; race; education.
Model 3 adjust for: sex; age; race; education; physical-activity; BMI; energy intake; hypertension; congestive heart failure; cancer or malignancy.
We also found that dietary Se intake has a line relation with telomere length in female patients with diabetes (Fig. 2); within the scope of 0–250 μg dietary Se intake, telomere length was longer following increased dietary Se intake.
Association between selenium and telomere length among diabetes in male and female.
Discussion
We used the NHANES database to recruit 878 patients with diabetes in the USA to investigate the relationship between dietary Se intake and telomere length. The findings showed a positive association between dietary Se intake and telomere length only in women with diabetes. In the dietary Se intake range of 0–250 μg, telomere length in the female population with diabetes increased with increasing dietary Se intake.
In the present study, we found an association between dietary Se intake and telomere length only in women with diabetes. These results were broadly consistent with those reported by Shu et al. (Reference Shu, Wu and Yang2). Considering the population particularity, gender, age, race, education, physical activity, BMI, energy intake, hypertension, congestive heart failure, cancer or malignancy-related covariates were controlled in a generalised linear model; thus, the sample information was less than that of Shu et al (Reference Shu, Wu and Yang2). Changes in telomere length in women may be influenced by oestrogen levels in their bodies(Reference Mayer, Brüderlein and Perner22). Oestrogen stimulates telomerase production and may prevent reactive oxygen species damage(Reference Gardner, Bann and Wiley23). In addition, women have better antioxidant and physiological properties of selenoproteins, which may reduce telomere attrition(Reference Ferguson, Karunasinghe and Zhu3,Reference Carrero, Stenvinkel and Fellström24) . Previous animal experiments have shown that female rats have a lower demand for Se than male rats(Reference Brown and Burk25,Reference Burk, Lawrence and Correia26) , which is related to sex differences in telomere attrition(Reference Shu, Wu and Yang2). However, the mechanism of action of sex on dietary Se intake and telomere length among diabetes remains unclear, and further studies are needed for confirmation.
Dietary Se intake is positively correlated with telomere length in patients with diabetes. This may be related to the following aspects. First, Se, an essential micronutrient for the human body, produces physiological characteristics in the form of selenoproteins and is absorbed by the body in the form of dietary Se. The anti-inflammatory properties of selenoproteins play a key role in telomere attrition, and the rapid replication of cells during inflammation accelerates cellular senescence and the extent of telomere attrition(Reference Zhang, Rane and Dai27). Second, the antioxidant defence properties of Se may prevent the development and progression of diabetes(Reference Siddiqi, Sun and Wu28), and ingestion of a certain Se content is beneficial for the population with diabetes(Reference Rajpathak, Rimm and Morris29). Third, long-term adherence to the Mediterranean diet can effectively reduce the risk of CVD and diabetes(Reference Martín-Peláez, Fito and Castaner30). In addition, the Mediterranean diet has anti-inflammatory and antioxidant properties that may affect telomere length, with a higher intake being associated with longer telomere length(Reference Canudas, Becerra-Tomás and Hernández-Alonso31). We found a line relationship between dietary Se intake and telomere length among diabetes within the range of 0–250 μg from a smoothed curve fit. The intake of dietary Se is protective in humans. Insufficient Se intake can decrease immune and cognitive function and even cause death(Reference Rayman1). Laclaustra et al. found in the National Health and Nutrition Examination Survey that excessive Se levels in the body increased the prevalence of diabetes(Reference Laclaustra, Navas-Acien and Stranges32).
This study has three limitations. First, this study was a cross-sectional survey and did not directly infer a causal relationship between dietary Se intake and telomere length in patients with diabetes. Second, our study shows that dietary Se intake is significantly associated with telomere length only within the range of 0–250 μg, and relevant experimental studies are needed to demonstrate in the future beyond which range whether they are still relevant. Finally, the final sample size was limited to 878 participants.
Conclusions
Therefore, the present study demonstrates that dietary Se intake is significantly associated with telomere length only present in the female population with diabetes in the USA. However, further prospective studies are required to confirm this finding.
Acknowledgements
This research received no external funding.
The authors declare no conflict of interest.
H-P. G., Q. Y., D-W. G. and W-X. H. contributed to the study design and writing; D-W. G. and Y-G. W. contributed to data analysis and discussion of the results; L-Z. D. and J-H. Z. contributed to article revision; J. W. and P. H. contributed to study design and manuscript revision. All authors have read and agreed to the published version of the manuscript.
