Dietary Selenium Intake and All-Cause Mortality in Diabetic Kidney Disease: A Dose-Response Relationship

doi:10.21203/rs.3.rs-4948239/v1

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Dietary Selenium Intake and All-Cause Mortality in Diabetic Kidney Disease: A Dose-Response Relationship

https://doi.org/10.21203/rs.3.rs-4948239/v1

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OBJECTIVE

Selenium plays a complex role in human health as an essential nutrient. Basic research has shown that selenium has antioxidant and anti-inflammatory effects. At present, the relationship between dietary selenium intake and mortality of diabetic kidney disease is unclear. This study affirmed the relationship between dietary selenium intake and all-cause mortality among adults with DKD.

RESEARCH DESIGN AND METHODS

From the National Health and Nutrition Examination Survey 2001-2014, 2,183 individuals with DKD were included in this analysis. The mortality rate was determined through the linkage of National Death Index records up to 31 December 2015. A Cox proportional hazards regression model was used to estimate the hazard ratios and 95% confidence intervals. The Kaplan Meier plotter is capable of analyzing the relationship between survival and selenium intake.

RESULTS

1063 deaths occurred during an average follow-up period of 8 years. A total of 298 deaths (54.880%) were observed in the lowest quartile of selenium intake, whereas 226 deaths (41.392%) were recorded in the highest quartile group. Adjusted for multiple variables, including demography factors, dietary factors, lifestyles, glucose control, and important comorbidities, selenium intake associated with a lower all-cause mortality risk in a dose-response relationship. Compared to the group with the lowest selenium intake, the hazard ratio(HR) of the highest group was 0.712 (95% CI 0.558,0.908) for mortality (P_trend= 0.021) with adjustment of potential confounding potential factors.

CONCLUSION

After adjusting for confounding variables, In people with DKD, dietary selenium intake was associated with a reduced mortality risk.

survival analysis

diabetic kidney disease

mortality

selenium intake

NHANES

Diabetes nephropathy, now customarily known as diabetic kidney disease, is the microvascular complications of diabetes, characterized by increased urinary protein and decreased glomerular filtration rate¹. DKD is one of the most rapidly developing chronic kidney diseases, resulting in end-stage renal disease and associated mortality. In U.S., about 40% of diabetes patients have kidney disease complications, which brings great pressure to public health². Compared with diabetes patients without kidney damage, the mortality rate of DKD patients increased by 30 times³. By understanding the underlying causes of DKD progression, doctors and patients can develop effective treatment strategies to prevent its onset and progression. Currently, improvements in lifestyle, such as diet and exercise are the primary means of preventing or delaying the progression of diabetic kidney disease⁴, combined with medication to maintain kidney function and regulate plasma glucose levels⁵.

Selenium regulates inflammation, B-cell function, and cell-mediated immunity through the cyclo-oxygenase and lipoxygenase pathways in anti-inflammatory defence^6,7. Additionally, Antioxidant enzymes require it as a component^8,9. Selenium deficiency is linked to diseases like diabetes, cardiovascular disease, autoimmune disorders, and certain cancers, particularly in developing countries¹⁰. The antioxidant properties of selenium are increasingly recognized for their role in diabetes, including type 2 diabetes^11–13. A link has been established between oxidative stress and the etiology, pathogenesis, and progression of DKD¹⁴. Selenium may confer benefits for individuals with diabetic kidney disease (DKD) through its non-classical function, which potentially provides protection against diabetes mellitus (DM). Research indicates that selenium exhibits insulin-mimetic properties, which may play a role in mitigating insulin resistance, facilitating normal glucose uptake, and regulating cellular glucose utilization¹⁵.

There has been research on how blood selenium levels affect diabetes, but the conclusions are controversial. T2DM is negatively associated with blood selenium, according to some studies^16–18, others found a positive correlation^19–21. According to other studies, there is no significant association between the two^22–25. Aside from that, selenium status and intake vary from country to country, which might explain the discrepancy in study results.

However, there is limited evidence regarding the direct impact of selenium in DKD patients with elevated oxidative stress and inflammatory status, leading to a higher risk of mortality. To fill these knowledge gaps, this study aims to prospectively examine the association between selenium intake and all-cause mortality risk in a nationally representative sample of DKD adults in the United States.

Participants in the study

The NHANES database collects health information and nutrition data of the the United States population. Its data are updated every two years in a cycle, and the database is free and open to the public, so researchers can download the data directly. Blood, urine, and other biological samples from participants are systematically collected and subjected to comprehensive analysis. Furthermore, the dataset encompasses an extensive array of questionnaires addressing demographic and socioeconomic factors, dietary and health-related issues, as well as physical examinations, which include both physiological measurements and laboratory tests.

We used the data from NHANES 2001–2014, which provided information on selenium intake. At first, patients with DM at enrollment were included, which resulted in a study sample of 6,536 subjects. The study defined diabetes mellitus as self-diagnosed by a physician, taking insulin or oral hypoglycemics, and using insulin supplements. Diagnostic criteria including: fasting blood glucose ≥ 126mg/dl; postprandial 2-h plasma glucose ≥ 200mg/dl from an oral glucose glucose tolerance test; glycated hemogloblin A1c (HbA1C) ≥ 6.5%. An impaired estimated glomerular filtration rate, an albumin-to-creatinine ratio greater than 30 mg/g, or both were used to diagnose DKD. There were 2378 participants who met the diagnostic criteria for DKD. The final analysis included 2,183 participants with DKD, excluding 13 without survival data, 162 without dietary intake data, and 20 without other covariates(Fig. 1).

Assessment of dietary selenium intake

The NHANES participants met the criteria to engage in two 24-hour dietary recall interviews. An in-person interview was conducted in the first interview, and a phone interview was conducted after four to ten days. Based on the two 24-hour recalls, the average dietary selenium intake was calculated. Intakes of dietary selenium were calculated using the Nutrients Database of the University of Texas Food Intake Analysis System. Then, a mean value of selenium intake was calculated based on two 24-hour dietary recall interviews..

Ascertainment of Mortality

Mortality was based on The National Death Index records are current up to December 31, 2015. Causes of death were determined based on ICD-10 codes.

Assessment of Covariates

The questionnaires collected sociodemographic data, smoking status, dietary intake, diabetes medication use, use of lipid-lowering therapy, and hypertension presence. A never smoker is operationally defined as an individual who has not consumed more than 100 cigarettes throughout their lifetime, while current smokers are characterized by over 100 cigarettes smoked in their lifetime and continuing to engage in smoking behavior. Former smokers are those who have quit smoking after smoking > 100 cigarettes. An individual can be diagnosed with hypertension by self-report or by measuring blood pressure during a physical examination. An average systolic blood pressure of 140mmHg or higher, an average diastolic blood pressure of 90mmHg or higher, and self-reported hypertension diagnosis qualify as hypertension. Those who answered "YES" to the following question ”Have you ever been told by a physician or a health professional that you had stroke?” was considered having stroke. The dietary inflammatory index (DII) is used to measure how forty-five specific nutrients contribute to inflammation²⁶. SII is calculated by multiplying the total peripheral platelet count by the neutrophil-to-lymphocyte ratio. Blood counts were done using automated hematology analyzers and are presented as cells per microliter²⁷. The NHANES Laboratory Medical Technologists Procedures Manual contains additional information regarding these measurements.

Statistical Analysis

Sample weights were applied to the analyses. Participants were divided into quartiles based on their selenium intakes. In this study, three models were used to calculate adjusted hazard ratios and 95% confidence intervals. An initial model was unadjusted model. Model 2 was adjusted for covariates including sex, age, smoking status, family income-to-poverty ratio, serum albumin levels, serum uric acid levels, dietary intake of phosphorus, Dietary Inflammatory Index score, Systemic Inflammatory Index score, serum iron levels, and history of stroke. Model 3 was adjusted to account for variables included in Model 2, in addition to hemoglobin A1c (HbA1c), hypertension, hypoglycemic treatment, and lipid-lowering therapy. The Kaplan Meier plotter is capable of assessing the correlation between dietary selenium intake and survival. The relationship between dietary selenium intake and all-cause mortality were explored by a smooth curve fitting. Analyses were conducted using R version 4.3.3, with P values less than 0.05 denoting statistical significance.

Subject Characteristics

The baseline characteristics of the participants were stratified into quartiles based on selenium intake and are detailed in Table 1. Among the 2,183 participants diagnosed with diabetic kidney disease (mean age: 65.87 years; 52.82% male). The median selenium intake, as represented by the interquartile range, was 87.7 mcg/day (IQR: 60.5–121.1 mcg/day). Participants with increased selenium intake demonstrated advanced age, greater family income, elevated hemoglobin and iron levels, reduced scores on the Dietary Inflammatory Index (DII) and Systemic Inflammatory Index (SII), as well as higher dietary phosphorus intake.

Table 1

Demographic characteristics of participants according to dietary selenium intake level
	Total	Quartile 1 < 60.4 mcg/d	Quartile 2 60.5–87.6 mcg/d	Quartile 3 87.7–121 mcg/d	Quartile 4 > 121 mcg/d	P
Characteristics
Patients, n	2183	548	543	546	546
Age, year						< 0.0001
<= 40	114(5.2)	19 (3.5)	31 (5.7)	51(9.3)	13(2.4)
40–60	520(23.8)	114(20.8)	138( 25.3)	183(33.5)	85(15.7)
> 60	1549(71.0)	415(75.7)	377(69.0)	312(57.1)	445(82.0)
Male sex	1153(52.8)	199(36.6)	272(49.6)	301(55.1)	381(69.8)	< 0.0001
Race						0.0353
Non-Hispanic White	940(43.6)	246(45.3)	239(43.6)	248(45.4)	207(37.9)
Non-Hispanic Black	550 (25.2)	144(26.5)	151(27.6)	126(23.1)	129(23.6)
Mexican American	398(18.2)	88(16.2)	94(17.2)	103(18.9)	113(20.7)
other	295(13.5)	65(12.0)	64(11.7)	69(12.64)	97(17.8)
Family income-to-poverty ratio						0.0018
<=1	479(21.9)	130(23.9)	124(22.6)	114(20.9)	111(20.3)
1–3	1179(54.0)	310(57.1)	303(55.3)	294(53.8)	272(49.8)
> 3	525(24.0)	103(19.0)	121(22.1)	138(25.3)	163(29.9)
Smoking states						0.010
Never smoker	997(45.7)	275(50.6)	252(46.0)	231( 42.3)	239(43.8)
Former smoker	833(38.2)	193(35.5)	224(40.9)	219(40.1)	197(36.1)
Now smoker	353(16.2)	75(13.8)	72(13.1)	96(17.6)	110(20.1)
HbA1c,%						0.0577
<= 7	1254(57.4)	330(60.8)	325(59.3)	310(56.8)	289(52.9)
> 7	929(42.6)	213(39.2)	223(40.7)	236(43.2)	257(47.1)
Stroke	279(12.8)	80(14.7)	72(13.1)	71(13.0)	56(10.3)	0.1895
Hypertension	1790(82.0)	453(83.4)	463(84.5)	442(81.0)	432(79.1)	0.0803
HGB, g/dl	13.7(12.5,14.8)	13.3(12.1 ,14.5)	13.4(12.3 ,14.7)	13.7 (12.5 ,14.8)	14.1 (12.9 ,15.3)	< 0.0001
ALB, g/dL	4.1 (3.9 ,4.3)	4.1(3.8 ,4.3)	4.1 (3.9 ,4.3)	4.1 (3.9 ,4.3)	4.1 (3.9 ,4.3)	0.3659
UA, mg/dl	6.0 (5.0 ,7.3)	6.2 (5.1 ,7.4)	6.10(5.0 ,7.4)	6.0 (5.0 ,7.2)	5.9 (4.9 ,7.1)	0.1468
Iron, µg/dl	73.0 (56.0 ,95.0)	68.0(52.0 ,91.0)	74.0 (56.0 ,95.0)	73.0 (56.0 ,94.0)	75.0(59.0 ,97.0)	0.0473
Phosphorus intake, mg	1047.0 (764.0 ,1443.0)	642.0 (460.0 ,842.0)	905.0 (764.0 ,1111.0)	1159.0 (968.0 ,1455.0)	1643.0 (1343.0 ,2056.0)	< 0.0001
DII	2.2 (0.8 ,3.2)	3.4 (2.4 ,4.0)	2.5 (1.4,3.4)	1.9 (0.7 ,2.8)	0.8(-0.6 ,1.9)	< 0.0001
SII	525.8 (363.0 ,769.0)	546.6 (361.5 ,793.3)	538.2 (372.7 ,773.4)	520.7 (373.9 ,770.0)	501.8 (344.3 ,735.0)	0.0415
Hypoglycemic treatment	1445(66.2)	277(53.4 )	295(57.3)	289(53.6)	259(46.8)	0.0536
Lipid-lowering therapy	1116(51.1)	357(65.9)	367(67.5)	363(65.1)	358(62.2)	0.5683
Mortality	1063(48.7)	298(54.9)	284(51.8)	255(46.7)	226(41.4)	< 0.0001

The continuous variables in this study do not follow a normal distribution and are represented by the median (Q1, Q3); Categorical variables are represented by number (percentage). Abbreviations: HGB = hemoglobin; ALB = albumin; UA = uric acid; DII = Dietary inflammatory index; SII = Systemic inflammatory index.

Association between dietary selenium intake and mortality

Table 2 presented the mortality hazard ratios for patients with diabetic kidney disease (DKD) based on quartiles of selenium intake levels. In model 1, the unadjusted model, the multivariate-adjusted hazard ratios (95% confidence intervals) for mortality ranged from < 60.4, 87.6–121.0, 121.0−715.8, to > 715.8 mcg/day, with values of 1 (reference), 0.817 (0.669, 0.998), 0.741 (0.611, 0.900), and 0.610 (0.496, 0.749) (P trend < 0.00001). In model 2, after adjusted for age(≤ 40, 40–60, > 60years), sex(male or female), family income-to-povery ratio(≤ 1.0, 1.0–3.0, > 3.0), smoking states(never smoker, fomer smoker, current smoker), hemoglobin(continuous), albumin(continuous), uric acid(continuous), dietary intake of phosphorus (continuous), Dietary Inflammatory Index (continuous), Systemic Inflammatory Index (continuous), serum iron (continuous), stroke (yes or no), from the lowest to the highest groups, the multivariate adjusted HRs (95% CIs) were 1 (reference), 0.810(0.670,0.979), 0.786(0.628,0.985), 0.714(0.560,0.909) for mortality (P for trend = 0.0150). Model 3 incorporated adjustments for all variables, including HbA1c (≤ 7% or > 7%), hypertension (presence or absence), hypoglycemic treatment (presence or absence), and lipid-lowering therapy (presence or absence), in addition to the adjustments made in Model 2, the multivariate-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for mortality ranged from 1 (reference) to 0.813 (0.669, 0.987), 0.789 (0.629, 0.989), and 0.712 (0.558, 0.908) across the lowest to highest intake groups, demonstrating a significant trend (P trend = 0.021). Furthermore, a smooth curve fitting graph illustrated a significant decrease in mortality risk with increasing selenium intake among patients with diabetic kidney disease (DKD) (overall P = 0.036; nonlinear P = 0.3944) (Fig. 2).

Table 2

All-cause mortality according to quartiles of dietary selenium intake among patients with DKD in NHANES 2001–2014
Exposure	Quartile 1	Quartile 2	Quartile 3	Quartile 4	P for trend
Range	< 60.4mcg/d	87.6–121.0 mcg/d	121.0-715.8mcg/d	> 715.8mcg/d
No. death/total	298/548	284/543	255/546	226/546
Model 1	1 (reference)	0.817(0.669,0.998)	0.741(0.611,0.900)	0.610(0.496,0.749)	< 0.00001
Model 2	1 (reference)	0.810(0.670,0.979)	0.786(0.628,0.985)	0.714(0.560,0.909)	0.015
Model 3	1 (reference)	0.813(0.669,0.987)	0.789(0.629,0.989)	0.712(0.558,0.908)	0.021

Date are presented as HR(95% CI) unless indicated otherwise.

Model 1: unadjusted model.

Model 2: adjusted for age( < = 40, 40–60, > 60years), sex(male or female), family income-to-povery ratio( < = 1.0, 1.0–3.0, or > 3.0), smoking states(never smoker, fomer smoker, current smoker), hemoglobin (continuous), albumin (continuous), uric acid(continuous), dietary intake of phosphorus (continuous), Dietary Inflammatory Index (continuous), Systemic Inflammatory Index (continuous), Serum iron (continuous), stroke (yes or no).

Model 3: Model 2 + HbA1c ( < = 7%, > 7%), hypertension(yes or no), hypoglycemic treatment(yes or no), lipid-lowering therapy(yes or no).

Kaplan-Meier survival curves with selenium intake categories showed that patients with the highest level of selenium intake had the highest likelihood of surviving(Fig. 3 ).

A consistent association was observed between total selenium intake and mortality when the analyses were stratified by age (> 60 years), sex, non-Hispanic Black race, estimated glomerular filtration rate (eGFR > 60 ml/min/1.73 m²), and glycated hemoglobin (HbA1c > 7%) (Table 3). No significant interactions were detected after adjustments for multiple testing were applied.

Table 3

Stratified analyses of the association between dietary selenium intake and all-cause mortality among patients with DKD in NHANES 2001–2014
	Dietary selenium intake
Characteristic	Quartile 1	Quartile 2	Quartile 3	Quartile 4	P trend	P interaction
Age, years						0.250
<= 40 (n = 114 )	ref	0.349(0.113,1.078)	0.455(0.148,1.399)	0.459(0.126,1.666)	0.609
40–60 (n = 520 )	ref	0.529(0.338,0.826)	0.668(0.393,1.133)	0.404(0.192,0.853)	0.059
> 60 (n = 1549 )	ref	0.918(0.709,1.189)	0.751(0.570,0.989)	0.688(0.487,0.973)	0.021
Sex						0.532
Male (n = 1030 )	ref	0.901(0.700,1.160)	0.710(0.503,1.004)	0.591(0.393,0.889)	0.009
Female (n = 1153)	ref	0.716(0.543,0.945)	0.742(0.543,1.014)	0.619(0.437,0.876)	0.014
Race						0.898
Non-Hispanic White (n = 940 )	ref	0.847(0.625,1.147)	0.799(0.563,1.134)	0.666(0.408,1.086)	0.109
Non-Hispanic Black (n = 550)	ref	0.686(0.481,0.977)	0.649(0.431,0.977)	0.444(0.276,0.715)	0.002
Mexican American (n = 398)	ref	0.929(0.622,1.387)	0.682(0.346,1.344)	0.737(0.389,1.396)	0.269
Other (n = 295 )	ref	0.769(0.390,1.514)	0.758(0.313,1.833)	0.905(0.377,2.174)	0.733
HbA1c,%						0.415
<= 7.0 (n = 1254 )	ref	0.797(0.611,1.040)	0.829(0.645,1.066)	0.588(0.418,0.827)	0.004
> 7.0 (n = 929 )	ref	0.790(0.553,1.129)	0.640(0.430,0.952)	0.635(0.403,1.000)	0.037
eGFR-EPI, ml/min·1.73m2						0.302
<= 60 (n = 1095)	ref	0.763(0.505,1.151)	0.930(0.623,1.387)	0.731(0.451,1.184)	0.419
> 60 (n = 1088 )	ref	0.926(0.756,1.135)	0.661(0.503,0.869)	0.629(0.443,0.893)	0.001

Data are presented as HR (95% CI). Adjusted for age( < = 40, 40–60, > 60years), sex(male or female), family income-to-povery ratio( < = 1.0, 1.0–3.0, or > 3.0),smoking states(never smoker, fomer smoker,current smoker), hemoglobin (continuous), albumin (continuous), uric acid(continuous), dietary intake of phosphorus (continuous), Dietary Inflammatory Index (continuous), Systemic Inflammatory Index (continuous), Serum iron (continuous), stroke (yes or no), HbA1c ( < = 7%, > 7%), hypertension(yes or no), hypoglycemic treatment(yes or no), lipid-lowering therapy(yes or no). The strata variable was not included in the model when stratifying by itself.

This study was the first study on dietary selenium intake and all-cause mortality among people with Diabetic Kidney Disease. There was a significant dose-response relationship between selenium intake and all-cause mortality. Traditional risk factors, including dietary and lifestyle factors, as well as hypoglycemic and lipid-lowering treatments, did not influence this association. The robustness of our findings was demonstrated through various stratified analyses.

Selenium was discovered in 1817 and was believed to be toxic to humans for almost 150 years. However, it was not until 1957, it was demonstrated that dietary selenium has the ability to protect rats from liver necrosis. As time has progressed, our understanding of the mechanisms by which selenium functions as a trace mineral nutrient in biological systems has advanced. Various physiological processes in humans, such as those involving the central nervous system, endocrine system, cardiovascular system, and immune system, necessitate sufficient levels of bioavailable selenium^28,29. An individual's selenium status can impact various immune system-related pathological conditions. Grains, seafood, vegetables, meat and nuts are good sources of selenium³⁰.

There was a negative correlation between selenium intake and mortality among diabetic kidney disease patients in our study, aligning with the findings of numerous prior prospective studies. Additionally, an investigation involving 1389 elderly participants demonstrated a positive relationship between plasma selenium level and all-cause mortality³¹. Within the InCHIANTI Study, adults in the lowest quartile of selenium showed significantly higher mortality risks than those in the highest quartile³². A cohort of 13,887 adult participants in the United States were monitored for a period of up to 12 years, revealing a association between selenium and mortality³¹. A meta-analysis concluded that Se supplementation, alone or in combination with other supplements, did not affect mortality rates statistically significantly³³.

Our study showed se intake may lower the risk of death in DKD patients, but its impact on diabetes incidence and prognosis is uncertain. Some studies suggest that selenium levels could decrease incidence of diabetes^34,35. On the other hand, some researchers have suggested that elevated levels of serum selenium may increase diabetes risk³¹, or that Se does not significantly influence T2D risk²⁰. A cross-sectional study identified a moderate negative correlation between dietary selenium intake and metabolic syndrome linked to diabetes³⁶. Se supplementation may led to improvements in glucose metabolism by decreasing fasting plasma glucose levels³⁷. In certain research investigations, insulin resistance has been linked to elevated selenium consumption.

The mechanism by which dietary selenium intake influences diabetes and its complications remains uncertain. Diabetic kidney disease (DKD) may be linked to dietary selenium intake through insulin resistance, for example, inflammation, and oxidative stress, all of which are significant contributors to its pathogenesis^38–41. Selenium exhibits a diverse array of pleiotropic properties, notably through its involvement in the activity of glutathione peroxidases dependent on selenium, which are pivotal in mitigating oxidative stress and inflammation⁴². Selenoproteins containing selenium may reduce levels of pro-inflammatory cytokines and markers of inflammation, including C-reactive protein, and mitigate oxidative stress. Previous research has indicated that sufficient selenium intake can benefit human health by enhancing metabolic function, boosting immune response, and slowing the aging process, which has been strongly linked to overall mortality rates^9,43. Another study has shown that selenium supplementation can increase the protective effects of antioxidant mixtures and decrease overall mortality rates⁴⁴. Research has demonstrated that Selenium enhances the phosphorylation and expression of eNOS protein, thereby safeguarding the vitality and migration capacity of endothelial cells⁴⁵. The decline in selenium levels during the development of DKD can be mitigated through selenium supplementation, which has been shown to ameliorate metabolic disturbances by mitigating oxidative stress and modulating inflammatory responses. However, the exact nature of these effects remains unclear, necessitating additional research.

Despite the study's strengths, there are several limitations to note. The observational study design precluded the establishment of causality. Furthermore, the study lacked detailed information on the severity of diabetic kidney disease, even after accounting for diabetes medication use and HbA1c levels. Additionally, the findings are specific to U.S. adults with diabetes, potentially limiting their generalizability. A genetic analysis of selenium metabolism was not conducted, suggesting a need for future research to explore potential interactions between diet and genes on mortality. Additionally, the limited statistical power of subgroup analyses necessitates cautious interpretation of the results. Lastly, residual and unknown confounding factors may still be present and should be considered in the interpretation of the findings.

The study found a correlation between increased dietary selenium intake and lower mortality in patients with diabetic kidney disease (DKD). In individuals with DKD, selenium supplementation may have potential benefits in preventing mortality.

Date availability statement

The survey data are publicly accessible on the Internet for data users and researchers worldwide at the following URL: http://www.cdc.gov/nchs/nhanes/.

Author contributions

Xiaona Wang: Responsibility for date analysis and manuscript writing. Dongyan Wang: research design and manuscript writing.

Funding

This study was supported by Qilu Traditional Chinese Medicine Advantage Specialist Cluster Project and Shandong Traditional Chinese Medicine Technology Project (Z-2023062T).

Conflicts of Interest

There were no conflicts of interest in this research.

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Dietary Selenium Intake and All-Cause Mortality in Diabetic Kidney Disease: A Dose-Response Relationship

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Abstract

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INTRODUCTION

Research design and methods

Participants in the study

Assessment of dietary selenium intake

Ascertainment of Mortality

Assessment of Covariates

Statistical Analysis

Results

Subject Characteristics

Association between dietary selenium intake and mortality

Discussion

Conclusion

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References

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