Abdelbaset-Ismail A, Hui X, Lin Q, Gu C, Xu J, Watson S, Cai L, Tan Y, Wintergerst KA. Serum elemental profiles and their associations with glycemic control in pediatric type 1 and type 2 diabetes. World J Diabetes 2026; 17(8): 122649 [DOI: 10.4239/wjd.122649]
Corresponding Author of This Article
Yi Tan, PhD, Professor, Phoenix Children’s Research Institute, Department of Child Health, University of Arizona College of Medicine, 475 N 5th St, Phoenix, AZ 85004, United States. yitan@arizona.edu
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Pediatrics
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Abdelbaset-Ismail A, Hui X, Lin Q, Gu C, Xu J, Watson S, Cai L, Tan Y, Wintergerst KA. Serum elemental profiles and their associations with glycemic control in pediatric type 1 and type 2 diabetes. World J Diabetes 2026; 17(8): 122649 [DOI: 10.4239/wjd.122649]
Ahmed Abdelbaset-Ismail, Xiaodan Hui, Chunjie Gu, Jason Xu, Sara Watson, Lu Cai, Yi Tan, Kupper A Wintergerst, Pediatric Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY 40202, United States
Ahmed Abdelbaset-Ismail, Xiaodan Hui, Yi Tan, Phoenix Children’s Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ 85004, United States
Qian Lin, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, United States
Sara Watson, Lu Cai, Yi Tan, Kupper A Wintergerst, Wendy Novak Diabetes Institute, Norton Children’s Hospital, Norton Children’s Endocrinology, University of Louisville School of Medicine, Louisville, KY 40202, United States
Sara Watson, Lu Cai, Kupper A Wintergerst, Center for Integrative Environmental Health Sciences, University of Louisville School of Medicine, Louisville, KY 40202, United States
Lu Cai, Yi Tan, Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States
Lu Cai, Department of Radiation Oncology, University of Louisville School of Medicine, Louisville, KY 40202, United States
Co-corresponding authors: Yi Tan and Kupper A Wintergerst.
Author contributions: Tan Y, Wintergerst KA, and Cai L conceived and designed the study; Tan Y, Wintergerst KA are the co-corresponding authors of this manuscript; Tan Y, Wintergerst KA, Cai L, and Watson S requested samples; Xu J, Hui X, Lin Q, Gu C, and Abdelbaset-Ismail A prepared samples and conducted inductively coupled plasma mass spectrometer trace elemental analysis; Abdelbaset-Ismail A, Xu J, Cai L, and Tan Y analyzed data; Abdelbaset-Ismail A, Tan Y, and Cai L wrote the manuscript; Hui X, Lin Q, Gu C, Wintergerst KA, Cai L, and Tan Y edited the manuscript; Wintergerst KA, Cai L, and Tan Y supervised this study; all authors have approved the final version of the manuscript.
AI contribution statement: The authors take full responsibility and accountability for all content of this manuscript. AI tools were not used to generate any part of the manuscript, produce original scientific data, perform independent scientific analyses, or draw scientific conclusions.
Supported by the National Institutes of Health (NIH), No. X01DK125891, No. R01HL125877, and No. P30ES030283; and the Jewish Heritage Fund for Excellence Research Enhancement Grant Program at the University of Louisville School of Medicine.
Institutional review board statement: The study protocol was also reviewed and approved by the University of Louisville institutional review board (approval No. 19.0542).
Informed consent statement: Written informed consent was obtained from parents/guardians, along with written assent from participants < 18 years of age, as required by local institutional review board regulations.
Conflict-of-interest statement: None of the authors has any conflict of interest relating to this study.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: The data supporting the findings of this study were obtained from the Pediatric Diabetes Consortium Registry. Data are not publicly available because of participant privacy and institutional restrictions but may be available from the corresponding author upon reasonable request and with appropriate approvals from the Pediatric Diabetes Consortium.
Corresponding author: Yi Tan, PhD, Professor, Phoenix Children’s Research Institute, Department of Child Health, University of Arizona College of Medicine, 475 N 5th St, Phoenix, AZ 85004, United States. yitan@arizona.edu
Received: April 27, 2026 Revised: June 11, 2026 Accepted: June 29, 2026 Published online: August 15, 2026 Processing time: 102 Days and 16.8 Hours
Abstract
BACKGROUND
Trace element dyshomeostasis has been implicated in the progression of diabetes mellitus (DM) in adults. However, data on elemental imbalances in children and adolescents with type 1 DM (T1DM) and type 2 DM (T2DM) remain limited.
AIM
To characterize serum elemental profiles and investigate their relationships with hemoglobin A1c (HbA1c) in diabetic children and adolescents.
METHODS
This observational study was conducted as a secondary analysis of 421 children and adolescents (221 with T1DM, 200 with T2DM) enrolled in the Pediatric Diabetes Consortium Registry. Demographics and clinical characteristics were briefly evaluated, and serum elemental profiles were analyzed and compared between the T1DM and T2DM and across demographic subgroups. Relationships between HbA1c and common serum elements or elemental ratios were assessed.
RESULTS
Serum magnesium (Mg), cobalt (Co), and antimony (Sb) levels were significantly lower in T2DM than in T1DM (all P < 0.0001), whereas copper (Cu) and zinc (Zn) levels were higher in T2DM compared to T1DM (both P < 0.0001). The Zn/iron (Fe) ratio was significantly lower in T1DM than in T2DM. By correlation analysis, in both T1DM and T2DM, HbA1c was positively associated with serum Cu (T1DM: ρ = 0.16, P = 0.02; T2DM: ρ = 0.31, P < 0.0001) and inversely associated with Zn/Cu ratio (T1DM: ρ = -0.21, P = 0.002; T2DM: ρ = -0.23, P = 0.001). In T1DM, HbA1c was also inversely associated with Zn (ρ = -0.16, P = 0.02) and the Zn/Fe ratio (ρ = -0.19, P = 0.01). In T2DM, HbA1c was positively associated with calcium and selenium, and inversely associated with Mg and barium. Significant ethnicity-related differences in the Zn/Cu ratio were observed in both T1DM and T2DM, and sex-related differences were identified in T2DM.
CONCLUSION
Youth with diabetes exhibit distinct serum elemental profiles, with significant alterations in Mg, Cu, Zn, Zn/Fe ratio, Co, and Sb. Multiple elements and elemental ratios were associated with HbA1c, including Cu, Zn, Zn/Fe, and Zn/Cu. This suggests that elemental dyshomeostasis may contribute to glycemic regulation and the pathophysiology of disease in pediatric diabetes. Further longitudinal studies involving healthy control groups are needed to clarify the clinical significance of these findings.
Core Tip: Trace elements play important roles in glucose metabolism, insulin action, and oxidative stress, yet their relationships to glycemic control in pediatric diabetes remain incompletely understood. This study comprehensively evaluated serum elemental profiles in children and adolescents with type 1 diabetes mellitus and type 2 diabetes mellitus. Distinct alterations in zinc, copper, magnesium, selenium, and trace-element ratios were identified, and several elements showed significant associations with glycated hemoglobin. These findings provide new insights into elemental dysregulation in pediatric diabetes and highlight potential biomarkers for glycemic control.
Citation: Abdelbaset-Ismail A, Hui X, Lin Q, Gu C, Xu J, Watson S, Cai L, Tan Y, Wintergerst KA. Serum elemental profiles and their associations with glycemic control in pediatric type 1 and type 2 diabetes. World J Diabetes 2026; 17(8): 122649
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by disturbances in glucose metabolism that lead to elevated blood glucose levels. DM primarily arises from either insufficient production or ineffective insulin action, resulting in type 1 DM (T1DM) and type 2 DM (T2DM), respectively. According to the Centers for Disease Control and Prevention’s National Diabetes Statistics Report, DM is the eighth leading cause of death in the United States[1]. Concurrently, DM increasingly affects children and adolescents worldwide, with a growing prevalence of both T1DM and early-onset T2DM, which is directly related to various factors such as genetic predisposition, obesity, and sedentary lifestyle changes[2,3].
Beyond disturbances in glucose metabolism, DM is also associated with the dyshomeostasis of essential trace elements and minerals, including zinc (Zn), copper (Cu), magnesium (Mg), and iron (Fe). These minerals play critical roles in maintaining various biological and biochemical processes in the body, particularly in insulin biosynthesis, secretion, and action, as well as in antioxidant defense and cellular metabolism[4-6]. Research into the role of trace elements in the etiology and pathogenesis of DM and its complications began in the 1960s[7] and has since increased significantly[8,9]. Emerging research and clinical evidence suggest that disruptions in mineral levels and homeostasis are implicated in the pathophysiology and progression of various diseases, including DM and its related complications. This occurs through mechanisms involving insulin resistance, β-cell dysfunction, and increased oxidative stress, which are hallmarks of both T1DM and T2DM[9-11]. Zn, for instance, plays a crucial role in insulin biosynthesis, storage, and secretion in pancreatic β-cells. Insulin is stored as Zn-stabilized hexamers within secretory granules, and the Zn transporter 8 facilitates Zn transport into these granules, thereby promoting insulin crystallization and maintaining β-cell function. Disruption of Zn homeostasis has been implicated in impaired insulin secretion, altered glucose metabolism, and increased susceptibility to diabetes[12-15]. In contrast, excess Cu may contribute to oxidative tissue injury through redox-dependent mechanisms[16]. Additionally, Mg is an essential cofactor for numerous enzymes involved in glucose metabolism and insulin signaling. Mg deficiency has been associated with impaired insulin receptor tyrosine kinase activity, reduced insulin sensitivity, defective glucose uptake, β-cell dysfunction, increased oxidative stress, and elevated cardiovascular risk in individuals with diabetes. Emerging evidence further suggests that inadequate Mg status may contribute to both the development and progression of diabetes-related complications[17-19]. However, the specific roles of certain minerals, such as selenium (Se) and Cu, in regulating glycemic control in individuals with T1DM and T2DM remain unclear[10,20,21].
In pediatric populations, mineral metabolism is influenced by various factors such as growth rate, hormonal changes during puberty, dietary patterns, and micronutrient absorption, which make it distinct from adult physiology[22]. However, most research on mineral metabolism in DM has primarily focused on adults, leaving a gap in pediatric-specific data, particularly regarding how mineral and trace element levels change with the duration of diabetes in children and adolescents. This gap limits our understanding of the causal relationships between mineral alterations and DM. Moreover, in the setting of DM, while most mineral supplementation-based trials, such as those involving Zn and Mg, have primarily focused on adults[23-27], pediatric trials are rare[28] and underpowered, limiting the availability of evidence-based guidance on supplementation or therapeutic interventions in children. Furthermore, adult DM-based studies often include diverse populations, whereas pediatric studies tend to lack ethnic and gender diversity, which may hinder the identification of population-specific mineral alterations associated with pediatric DM. Recent metallomic studies have demonstrated that multiple trace elements may interact synergistically rather than act independently, and that alterations in trace-element ratios, such as Zn/Cu, may better reflect metabolic disturbances than individual mineral concentrations alone. However, comprehensive metallomic analyses in pediatric diabetes remain limited, particularly among ethnically diverse populations and across different diabetes subtypes[8,29].
This knowledge gap hinders the development of evidence-based guidelines for diagnosing and managing DM in youth. Filling this gap in understanding mineral alterations in children with diabetes can yield important insights into the pathogenesis and progression of DM. Also, it may help identify potential nutritional or therapeutic interventions that could enhance glycemic control and reduce long-term complications. Thus, the aim of this study was to characterize serum elemental profiles in children and adolescents with T1DM and T2DM, with particular emphasis on sex- and ethnicity-related differences. In addition, this study aimed to evaluate specific trace elements and their ratios, including Zn/Cu and Zn/Fe. We also sought to investigate potential associations between common serum minerals and glycemic control, as indicated by hemoglobin A1c (HbA1c) levels. Ultimately, this study seeks to identify specific micronutrient imbalances that may contribute to disease pathophysiology, metabolic dysregulation, and long-term complications in youths with diabetes.
MATERIALS AND METHODS
Ethics statement
This observational study was conducted as a secondary analysis using participants’ samples from the Pediatric Diabetes Consortium (PDC) Registry. The PDC protocol was approved by the Institutional Review Boards (IRBs) at each participating center. Written informed consent was obtained from parents/guardians, along with written assent from participants < 18 years of age, as required by local IRB regulations. The study protocol was also reviewed and approved by the University of Louisville IRB (approval No. 19.0542). Although the patient data used in this secondary analysis were acquired from the PDC Registry, the analyses, interpretations, and conclusions presented here belong solely to the authors and have not been reviewed or endorsed by the PDC. Because this study was conducted as a secondary analysis of samples and data obtained from the PDC Registry, the final sample size was determined by the availability of eligible participants and serum specimens.
Patients
This study involved 421 randomly selected children and adolescents, including 221 with T1DM and 200 with T2DM. Participants were eligible for enrollment in this study if they were < 21 years of age and had a diagnosis of T2DM according to the American Diabetes Association criteria. Diabetes diagnosis required one or more of the following: HbA1c ≥ 6.5% (≥ 48 mmol/mol), random plasma glucose > 200 mg/dL (11.1 mmol/L), 2-hour plasma glucose during an oral glucose tolerance test ≥ 200 mg/dL (11.1 mmol/L), or fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L). T2DM classification, once diabetes was confirmed, required the absence of diabetes-associated autoantibodies, including insulin autoantibody, glutamic acid decarboxylase antibody, islet antigen-2 antibody, islet cell antibody, and Zn transporter 8 antibody. In cases where autoantibody testing was not available at diagnosis, T2DM was defined by an elevated fasting C-peptide level (above the laboratory reference range) and/or the absence of insulin requirement 6 months after diagnosis. Additionally, participants were required to have a weight percentile ≥ 85% for age and sex, either at the time of diagnosis or before weight loss associated with undiagnosed diabetes[30,31]. A separate cohort consisting of youth with newly diagnosed T1DM. Detailed characterization of the PDC T1DM New Onset registry has been described previously[32,33]. Information collected at the presentation included demographic variables (age, sex, race/ethnicity), anthropometric variables [height, weight, body mass index (BMI) percentile, BMI Z-score], clinical variables (duration of diabetes, systolic and diastolic blood pressure), and metabolic variables [glucose, HbA1c, and blood urea nitrogen (BUN)]. BMI, computed from the closest height and weight, was measured by the health care provider, and the BMI percentile for age and gender was calculated using the 2000 Centers for Disease Control and Prevention growth charts for the United States[34]. Ethnicity data were obtained directly from the PDC Registry using standardized demographic data collection procedures. The ethnicity classification (Hispanic/non-Hispanic) was recorded as part of the registry dataset and categorized as Hispanic or non-Hispanic for subgroup analyses. These data were collected from patients’ medical records or from interviews with participants and/or parents.
Inductively coupled plasma mass spectrometer trace metal analysis
For the analysis, serum samples (100 μL each) were digested in 0.5 mL of 70% trace metal-grade nitric acid at 65 °C on an incubation shaker for 4 hours. Upon completion of the digestion process, the samples were allowed to cool to room temperature, then filtered and adjusted to a final nitric acid concentration of 4% by adding Milli-Q deionized water. The concentrations of each metal element were determined using an X Series II quadrupole inductively coupled plasma mass spectrometer (Thermo Fisher Scientific), which was equipped with an ESI SC-2 autosampler (Elemental Scientific, Inc.) for sample injection. During the injection process, internal standards, including bismuth, indium, lithium, scandium, terbium, and yttrium (all from Inorganic Ventures), were incorporated into each sample. This combination facilitated the correction of measurement drift, thereby enhancing the overall accuracy of the results. Each sample was analyzed in triplicate, and the elemental concentrations were quantified and reported in nanograms per milliliter (ng/mL). Values below the cut-off concentration threshold were regarded as non-detectable.
Statistical analysis
Continuous variables were initially inspected for normality using the Shapiro-Wilk test. Variables that were not normally distributed between the two independent groups were compared using the Mann-Whitney U test. Categorical variables, including sex and ethnicity, were analyzed using the binomial and χ2 tests, respectively. Descriptive statistics for continuous variables are presented as medians with interquartile ranges, whereas categorical variables are reported as n (%). Spearman’s rank correlation coefficient (ρ) was calculated to examine the associations of serum HbA1c and diabetes duration with demographic, laboratory, and metabolic variables. All statistical tests were two-tailed, and a P value of < 0.05 was considered statistically significant. Data analyses were performed using GraphPad Prism version 9.0 (GraphPad Software, San Diego, CA, United States) and SPSS Statistics version 20.0 (IBM Corp., Armonk, NY, United States).
RESULTS
Characteristics of T1DM and T2DM study populations
The demographic and clinical characteristics of children and adolescents with T1DM and T2DM are summarized in Table 1. A total of 421 pediatric patients with diabetes were analyzed, comprising 221 with T1DM (52.5%) and 200 with T2DM (47.5%). T2DM participants were significantly older than those with T1DM, with median ages of 15.37 years and 12.49 years, respectively (P < 0.0001). Furthermore, a greater proportion of T2DM patients were female (65.5% of the cohort) than of T1DM patients (42.5%; P = 0.02). Conversely, patients with T1DM were more likely to be male, representing 57.5%, compared to 34.5% in the T2DM cohort (P < 0.0001).
Table 1 Characteristic features of children and adolescents with type 1 diabetes mellitus and type 2 diabetes mellitus, n (%).
The ethnic distribution among patients with T2DM differed significantly from that among patients with T1DM. Notably, T2DM patients were predominantly Hispanic and Black/African American, compared to T1DM patients (P < 0.0001 for both). In contrast, the T1DM group displayed a higher prevalence of White individuals compared to T2DM patients (P < 0.0001).
Regarding anthropometric measures, T2DM patients had significantly greater body mass, as evidenced by higher median weight, height, BMI percentile, and BMI Z-score than T1DM patients (P < 0.0001 for all comparisons). T1DM patients exhibited a longer median duration of diabetes (P < 0.0001). However, these patients also had higher HbA1c (P < 0.0001) and fasting glucose (P < 0.0001). Serum BUN levels were also higher in the T1DM patients (P < 0.0001) compared to T2DM patients.
Comparison of serum elemental levels in pediatric T1DM and T2DM
Serum elemental levels in pediatric patients with T1DM and T2DM were analyzed and compared (Table 2). T1DM patients had significantly lower serum Cu and Zn levels than T2DM patients (P < 0.0001 for both). The serum Zn/Fe ratio was also significantly lower in T1DM compared to T2DM, but the Zn/Cu ratio was not significantly different between these two groups. Serum antimony (Sb) was significantly higher in T1DM than in T2DM (P = 0.0001). Serum Mg and cobalt (Co) were significantly lower in T2DM than in T1DM patients (both P < 0.0001). Given that it did not differ significantly, serum Fe was slightly lower in T2DM than in T1DM patients (P = 0.1). Serum barium (Ba) was at the borderline of significance and was found to be higher in T2DM than in T1DM (P = 0.058). There were no significant differences observed in serum sodium (Na), potassium (K), calcium (Ca), Se, manganese (Mn), aluminum, or nickel levels between the two types of DM.
Table 2 Statistical analysis of elemental concentrations in serum samples of children and adolescents diagnosed with type 1 diabetes mellitus and type 2 diabetes mellitus, median (interquartile range).
By subgroup analysis of T1DM pediatric patients by ethnic background, participants with T1DM included 60 (27.2%) Hispanic and 153 (69.2%) non-Hispanic children (Table 3). Of note, 8 patients (3.6%) of unknown ethnicity were excluded from the analysis. No significant differences were observed between the two subgroups in median age, weight, height, BMI percentile, BMI Z-score, blood pressure, duration of diabetes, HbA1c%, glucose levels, or most serum electrolytes and trace elements. Notably, however, non-Hispanic patients had significantly lower median serum Na levels (298.05 mg/dL vs 303.2 mg/dL, P = 0.01) and a lower median serum Zn/Cu ratio (0.64 vs 0.74, P = 0.0002) than Hispanic patients. In contrast, median serum Cu levels in non-Hispanic patients were significantly higher compared to Hispanic patients (113.6 μg/dL vs 97.25 μg/dL, P < 0.0001). There were no significant differences noted for other serum elements, including Zn, the Zn/Fe ratio, Fe, Se, Mn, and Ba, or for other assessed clinical and metabolic parameters. These findings suggest that, while most clinical and biochemical characteristics are comparable between Hispanic and non-Hispanic T1DM patients, there may be subtle differences in serum trace mineral status deserving of further investigation.
Table 3 Comparative analysis of Hispanic and non-Hispanic subpopulations with type 1 diabetes mellitus.
Sex-based differences in pediatric patients with T1DM
We then compared anthropometric and clinical characteristics, as well as serum elemental levels, between male and female patients with T1DM (Table 4). Patients with T1DM included 127 males (57.5%) and 94 females (42.5%). The median age at presentation was comparable between both sexes (13.03 years for males vs 12.06 years for females, P = 0.2).
Table 4 Comparative analysis of male and female subpopulations in type 1 diabetes mellitus.
While not statistically significant, female patients had higher median BMI percentiles (81.88 vs 71.13, P = 0.1) and BMI Z-scores (0.91 vs 0.56, P = 0.1), suggesting increased adiposity in females. The median durations of diabetes, HbA1c%, and blood glucose levels were comparable across both sexes, suggesting comparable disease duration and metabolic control. Median serum BUN levels were higher in males compared to females (15.0 mg/dL vs 12.0 mg/dL, P = 0.001). There were no differences detected in median serum levels of Na, K, Mg, Ca, Fe, Cu, Zn, Se, Mn, and Ba, as well as Zn/Fe and Zn/Cu ratios between male and female patients.
Ethnic differences in T2DM pediatric patients
A detailed analysis comparing Hispanic and non-Hispanic pediatric patients with T2DM is depicted in Table 5. In this cohort, 109 (54.5%) patients were Hispanic, and 89 (44.5%) were non-Hispanic. Of note, 2 patients (1%) with unknown ethnicity were excluded from the analysis. The parameters, including age, BMI percentile, BMI Z-score, blood pressure, duration of diabetes, BUN, HbA1c%, and fasting glucose levels, showed comparable results across both subgroups. However, non-Hispanic patients had significantly higher median body weight (99.9 kg vs 90.5 kg, P = 0.01) and height (168.6 cm vs 162.7 cm, P < 0.001) than Hispanic participants. Although median serum Zn and Cu levels were comparable in non-Hispanic vs Hispanic patients (Zn: 77.95 μg/dL vs 82.98 μg/dL, P = 0.08; Cu: 124.90 μg/dL vs 121.20 μg/dL, P = 0.09), the median serum Zn/Cu ratio was significantly lower in non-Hispanic patients (0.62 vs 0.68, P = 0.01). Hispanic T2DM patients had lower median serum Mn (1.42 μg/L vs 2.89 μg/L, P = 0.01) and Ba levels (2.88 μg/L vs 6.17 μg/L, P < 0.001) compared to non-Hispanic patients. These variations may indicate differing environmental exposures or dietary patterns that were not captured in clinical records. No differences were detected in serum levels of Na, K, Mg, Ca, Fe, and Se between the two populations. The median serum Zn/Fe ratio, albeit not statistically significant, was lower in non-Hispanic than in Hispanic patients (0.86 vs 1.08, P = 0.32).
Table 5 Comparative analysis of Hispanic and non-Hispanic subpopulations diagnosed with type 2 diabetes mellitus.
Sex-based differences in pediatric patients with T2DM
Among the 200 children and adolescents with T2DM, 69 (34.5%) were males, and 131 (65.5%) were females. As shown in Table 6, males were significantly older than female patients at presentation, with a median age of 16.22 years vs 15.18 years for females (P = 0.003). Male patients also had significantly higher median weight (105.1 kg vs 87.9 kg, P < 0.0001), height (174.2 cm vs 162.5 cm, P < 0.0001), BMI Z-score (2.42 vs 2.16, P = 0.002), and BMI percentile (99.23 vs 98.46, P = 0.002), indicating a greater overall body mass and stature compared to female patients. Male patients had a shorter median duration of diabetes than females (1.61 years vs 2.2 years, P = 0.03), but no significant differences were observed in glycemic control markers (HbA1c) or blood glucose levels. Higher median serum BUN levels were observed in males than in females (12.0 mg/dL vs 10.0 mg/dL, P = 0.02). Female patients displayed lower median serum levels of Na (296.04 mg/dL vs 301.67 mg/dL, P = 0.02), Ca (8.96 mg/dL vs 9.35 mg/dL, P = 0.02), and Mg (1.87 mg/dL vs 1.92 mg/dL, P = 0.05) compared to male patients. Additionally, females had significantly lower median serum Zn levels (78.38 μg/dL vs 82.57 μg/dL, P = 0.01), while Cu levels were slightly higher (121.5 μg/dL vs 122.9 μg/dL, P = 0.01), resulting in a significantly lower serum Zn/Cu ratio in females (0.69 vs 0.63, P = 0.001) compared to male patients.
Table 6 Comparison between the male and female subpopulations within type 2 diabetes mellitus.
In summary, despite showing comparable glycemic profiles, female patients with T2DM exhibited distinct differences in serum micronutrient levels, particularly lower Zn levels and lower Zn/Cu ratio, compared to their male counterparts. This highlights the importance of considering sex-based differences in the management and treatment of pediatric patients with T2DM.
Altogether, the Zn/Cu ratio demonstrated demographic variability in the present study. Significant differences in the Zn/Cu ratio were observed between Hispanic and non-Hispanic participants in both T1DM (P = 0.0002) and T2DM (P = 0.01). In contrast, no significant sex-related difference was observed among patients with T1DM (P = 0.70), whereas a significant difference was identified between male and female participants with T2DM (P = 0.001). These findings suggest that demographic factors, particularly ethnicity and sex in T2DM, may influence the Zn/Cu ratio and should be considered when interpreting its association with glycemic control.
Association analysis in pediatric patients
Association patterns of clinical variables and common serum elements with HbA1c in T1DM, T2DM, and overall DM participants were analyzed as outlined in Table 7 and Figure 1.
Figure 1 Correlation analysis between serum elements and glycemic control.
A: Representative scatter plots showing correlations between hemoglobin A1c (HbA1c) levels (%) and serum concentrations of zinc (Zn) (μg/dL), copper (Cu) (μg/dL), and the Zn-to-Cu (Zn/Cu) ratio in pediatric patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), as well as in the overall diabetes cohort; B: Representative scatter plots showing correlations between HbA1c levels (%) and serum concentrations of magnesium (mg/dL), calcium (mg/dL), and selenium (μg/L) in pediatric patients with T1DM and T2DM, as well as in the overall diabetes cohort. The plots include linear regression lines for T1DM (blue), T2DM (red), and overall diabetes (black), with each point representing an individual participant. Spearman’s correlation coefficient (ρ) and significance values (P) are also included, with thresholds set at P < 0.05. T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus; DM: Diabetes mellitus; HbA1c: Hemoglobin A1c; Zn: Zinc; Cu: Copper; Mg: Magnesium; Ca: Calcium; Se: Selenium.
Table 7 Correlation analysis among children and adolescent patients with type 1 diabetes mellitus and type 2 diabetes mellitus, and the overall diabetic population.
Association analysis in pediatric patients with T1DM
HbA1c was positively associated with age (ρ = 0.17, P = 0.01), glucose levels (ρ = 0.21, P = 0.002), diastolic blood pressure (ρ = 0.24, P < 0.001), and serum Cu (ρ = 0.16, P = 0.02). HbA1c was inversely associated with serum Zn (ρ = -0.16, P = 0.02), the Zn/Fe ratio (ρ = -0.19, P = 0.01), and the Zn/Cu ratio (ρ = -0.21, P = 0.002). These findings suggest a potential connection between inadequate glycemic control and pro-inflammatory or oxidative micronutrient profiles in T1DM.
Association analysis in pediatric patients with T2DM
HbA1c showed a robust positive correlation with glucose levels (ρ = 0.65, P < 0.0001), diastolic blood pressure (ρ = 0.24, P < 0.001), and serum levels of Cu (ρ = 0.31, P < 0.0001), and was positively correlated with Se (ρ = 0.18, P = 0.01), and Ca (ρ = 0.16,P = 0.03). However, it was inversely associated with serum Mg (ρ = -0.20, P = 0.004), the Zn/Fe ratio (ρ = -0.14, P = 0.05), the Zn/Cu ratio (ρ = -0.23, P = 0.001), and Ba (ρ = -0.16, P = 0.05).
Association analysis in overall pediatric DM patients
HbA1c was inversely associated with the BMI Z-score (ρ = -0.22, P < 0.0001). HbA1c was positively associated with serum fasting glucose (ρ = 0.49, P < 0.0001) and diastolic blood pressure (ρ = 0.14, P = 0.005). HbA1c was positively associated with serum Cu (ρ = 0.17, P = 0.001), Fe (ρ = 0.16, P = 0.001), and Se (ρ = 0.13, P = 0.01). Additionally, HbA1c showed inverse association with the serum Zn/Cu ratio (ρ = -0.2, P < 0.0001), the Zn/Fe ratio (ρ = -0.19, P = 0.0001), and Ba (ρ = -0.15,P = 0.01). These patterns suggest that poorer glycemic control is associated with alterations in serum mineral and trace element balance in pediatric patients with DM.
Collectively, these associations verify the significance of altered mineral and trace element homeostasis, particularly the Zn/Cu ratio for assessing glycemic control and disease burden in pediatric diabetics, but not as classification criteria for diabetes types. Most statistically significant correlations observed in this study were modest in magnitude (ρ = 0.20-0.39), and no very strong correlations were identified.
DISCUSSION
This study identifies significant alterations in elemental profiles among pediatric patients with T1DM and T2DM, as well as within their ethnic and sex diversity. Moreover, our correlation analysis revealed several significant associations between serum mineral alterations and glycemic control (HbA1c) in youths with T1DM and T2DM.
Our analysis indicated that, in addition to lower serum Mg levels in T2DM compared to T1DM, serum Mg was also negatively associated with HbA1c in T2DM patients. This finding is consistent with a cross-sectional study that demonstrated that serum Mg levels are significantly and negatively correlated with the risk of obesity and abdominal obesity in elderly Chinese adults with T2DM[35]. In children and adolescents with T1DM, two studies have shown that hypomagnesemia is associated with an increased risk of poor glycemic control and diabetes development[36,37]. Another recent study using Mendelian randomization found that Mg was associated with a negative causal effect on the risk of T1DM[38]. Therefore, low blood Mg level has been a recognized factor contributing to insulin resistance and has been associated with an elevated risk of diabetic complications[19,39]. Mg is important for glucose uptake and carbohydrate metabolism. It plays a crucial role in insulin activity by serving as a cofactor in the insulin signaling cascade. Low intracellular Mg levels impair tyrosine kinase activity, leading to reduced insulin action and increased insulin tolerance[40]. Therefore, Mg deficiency may exacerbate T1DM and T2DM, and supplementation may improve these conditions. This concept was supported by animal studies showing that dietary Mg intake via drinking water (50 mg/mL) for 6 weeks improved fasting blood glucose levels, enhanced mitochondrial function, and reduced oxidative stress in diabetic mice[41]. The low serum Mg in these pediatric patients could be attributed to low Mg intake or increased urinary Mg loss, as previously suggested[19]. Notably, the lower Mg levels observed in patients with T2DM than with T1DM (Table 2) further suggest a potential differential role of Mg in the pathogenesis of these two types of diabetes.
Zn is a vital micronutrient that plays a crucial role in metabolism. It regulates more than 300 enzymes that are essential for protein folding, gene expression, and the production and neutralization of reactive oxygen species. Its importance in these biological processes highlights the necessity of maintaining adequate Zn levels for overall health. Recent studies have further demonstrated that Zn functions as a signaling molecule regulating insulin synthesis, secretion, and intracellular metabolic pathways. Alterations in Zn transporter activity, particularly Zn transporter 8, have been associated with impaired β-cell function and increased susceptibility to diabetes. These findings provide additional mechanistic support for the inverse association between serum Zn levels and HbA1c observed in the present study[13,42]. In this study, compared to children with T2DM, serum Zn levels were significantly lower in youth with T1DM (Table 2) and were also negatively correlated with HbA1c (Figure 1). Comparably, a prior study of 25 children with T1DM and 13 healthy controls concluded that lower serum Zn levels were found in those with diabetes compared to healthy controls[43]. Additionally, a more recent study aimed to investigate the role of Zn in T2DM pathogenesis through a combination of bioinformatics analysis and molecular docking in adult participants. The authors found that Zn levels were significantly lower in 50 T2DM patients, with or without nephropathy, compared to 15 controls[44]. Thus, Zn may serve distinct physiological functions in each type of diabetes. These findings are supported by the important role of Zn in the proper processing, storage, secretion, and function of insulin within mammalian pancreatic cells. Furthermore, Zn deficiency can impair immune function and intensify cytokine-induced damage during autoimmune attacks, ultimately leading to the destruction of islet cells in individuals with T1DM[12,14]. We primarily attributed the Zn deficiency observed in children with diabetes to impaired Zn absorption in the gastrointestinal tract due to diabetes-related alterations. Additionally, hyperglycemia and metabolic disturbances associated with diabetes can increase urinary Zn excretion and decrease renal Zn reabsorption[45]. Relatedly, a recent study assessed serum and urine Zn levels in individuals with pre-diabetes and diabetes in Northeast China. The findings revealed that serum Zn levels were significantly lower, whereas urinary Zn levels were notably elevated in both T1DM and T2DM[46]. As shown in adult individuals with diabetes, Zn supplementation could enhance serum Zn levels and provide therapeutic benefits by improving both insulin sensitivity and secretion[23,26,27]. Previous studies in animals have shown that Zn chloride administration in diabetic rats is associated with notable improvements in serum glucose concentrations and in markers of oxidative damage in the pancreas and retina[47,48]. On the other hand, a study compared serum Zn levels in 30 children with T1DM with those in 30 age- and sex-matched healthy controls. The authors found no significant differences or correlations between serum Zn levels and fasting blood glucose, HbA1c, or duration[49]. These unclear findings may be due to the small sample size. Nonetheless, expanding the sample size as we used in our study could provide more comprehensive observations.
Cu plays a vital role in various biological functions and enzymatic processes, including activation of metalloenzymes and interaction with glutathione[50,51]. It is important to note that both insufficient and excessive Cu levels can be toxic to cells[52]. As an antioxidant, Cu is a key component of Cu/Zn superoxide dismutase, which is primarily known for its role in scavenging free radicals in cells[53]. Despite emerging evidence suggesting that Cu may also function as a pro-oxidant[54], the precise role of Cu in glycemic control among individuals with T1DM and T2DM remains uncertain. Alterations in Cu homeostasis have been noted in DM[55], with several studies reporting a connection between Cu levels and diabetes-related complications[56-58]. Elevated serum Cu levels have been reported in adults with T1DM or T2DM; however, no significant differences in serum Cu levels have been observed between these two groups[59]. Additionally, the high intake of Cu has been linked to oxidative stress and renal dysfunction in diabetic models[60]. However, some studies suggest that lower Cu levels, particularly when using Cu-chelating agents, can improve cardiac function in models of diabetic cardiomyopathy[61]. Despite this, Cu deficiency might play a role in vascular dysfunction and insulin resistance, which are commonly observed in individuals with diabetes[62]. In the present study, we found that serum Cu levels were higher in children with T2DM than in those with T1DM. Several recent studies have reported significant associations between serum Cu concentrations and glycemic status, inflammation, and diabetes-related complications. Elevated Cu levels have been linked to increased oxidative stress and chronic inflammatory activity, both of which contribute to insulin resistance and metabolic dysfunction. These observations are consistent with our finding that serum Cu levels were positively associated with HbA1c in both T1DM and T2DM children[62-64]. Furthermore, significant differences in serum Cu levels were observed between patients with T1DM and T2DM, suggesting that elevated Cu levels in children with T1DM may represent a compensatory response to the oxidative stress known to be markedly elevated in diabetes[65]. In this regard, as Cu levels are influenced by the body’s reserves of other micronutrients and considering its dual role as both an antioxidant and a pro-oxidant, further research is warranted to determine appropriate cutoff values for adequate Cu status in plasma or serum, in conjunction with glycemic control markers, in individuals with T1DM and T2DM.
The observed imbalance of Cu and Zn levels in this study likely contributes to the significantly reduced Zn/Cu ratios present in both types of pediatric diabetes. This was evident by the strong inverse association between the Zn/Cu ratio and HbA1c in both types of diabetes, supporting their potential utility as biomarkers for glycemic control in children with T1DM or T2DM. It is noteworthy that the serum Zn/Cu ratio may be a more accurate predictor of health status than either serum Zn or Cu levels[46]. Compiling evidence indicates that alterations in trace metal ratios, such as Zn/Cu, can substantially affect the development of chronic diseases, including diabetes. A low Zn/Cu ratio is associated with an imbalance between these trace elements and has been proposed as a potential biomarker for metabolic syndrome and diabetes-related complications. Evidence supporting this notion suggests that a reduced Zn/Cu ratio is commonly associated with a higher risk of developing diabetes[66,67].
The Zn/Cu ratio showed no significant differences between individuals with T1DM and those with T2DM. Consequently, this result should be interpreted with caution and not considered a distinguishing factor between the two diabetes types. Nevertheless, significant inverse associations were observed between the Zn/Cu ratio and HbA1c levels in both T1DM and T2DM patients. This finding suggests a potentially important relationship with glycemic regulation, rather than serving as a classification criterion for diabetes types.
Furthermore, in this study, a subgroup analysis comparing Hispanic and non-Hispanic children within each T1DM and T2DM cohort revealed that serum Zn/Cu ratios were significantly lower among non-Hispanic than among Hispanic children. We explain that the differences in Zn/Cu ratios observed in our data were due to altered serum Cu levels in non-Hispanic T1DM patients and altered Zn levels in non-Hispanic T2DM patients. These results provide important insight into how ethnic background may affect biochemical and mineral balance in children with diabetes; nonetheless, further studies are needed to determine the clinical significance of these findings, particularly given the higher prevalence of T1DM observed among non-Hispanic children. Furthermore, because a higher prevalence of T2DM was observed among female children, we found that female children with T2DM exhibited lower Zn and Zn/Cu ratios than male children. The variations in trace mineral balance observed between genders in T2DM may be attributed to hormonal factors, including estrogen, which tends to be present at low, fluctuating levels during childhood and adolescence. This hormonal variability can influence metal-binding proteins and impact the expression of intracellular free Zn and Zn transporters[68,69], which, in relation to glycemic control markers, warrant further exploration, especially in patients with T2DM.
In line with our data, prior studies have shown in adults that elevated serum or plasma concentrations of Cu or the Cu/Zn ratio are associated with increased oxidative stress and inflammatory responses, consequently raising the risk of developing T2DM[67-69]. The mechanisms linking a higher Cu/Zn ratio to increased diabetes risk are not fully elucidated; however, it is suggested that both Cu and Zn are vital for the optimal function of antioxidant enzymes. An imbalance in their ratios may compromise the antioxidant defense system and exacerbate the effects of free radicals dependent on these metals. Hence, this could contribute to the progression of DM and its associated complications[70]. In addition, dysregulation of these trace elements may adversely affect pancreatic islet function, thereby initiating and exacerbating the pathological processes that lead to T2DM and its complications[71]. A recent cross-sectional study involving patients with T2DM concluded that elevated serum levels of soluble tumor necrosis factor-alpha receptor 1, combined with an increased Cu/Zn ratio, may be associated with a higher prevalence of diabetic kidney disease[72]. It has also been suggested that children and adolescents with acute and chronic health conditions are at an elevated risk for developing increased Cu/Zn ratios, which are related to their altered nutritional, infectious, and inflammatory statuses[10].
Moreover, we found a positive association between HbA1c and Se in T2DM patients, indicating a potential involvement of micronutrients beyond Zn and Cu in the pathogenesis of T2DM. However, findings from human-based adult studies on Se and diabetes have been controversial. Some studies have reported lower serum Se concentrations in patients with diabetes compared to non-diabetic controls[20,21]. Conversely, a cross-sectional analysis conducted by the National Health and Nutrition Examination Survey found that higher serum Se concentrations were correlated with a higher prevalence of diabetes in United States adults, as evidenced by elevated fasting plasma glucose and glycosylated hemoglobin levels[73,74]. Additionally, a recent analysis of data from the Nutritional Prevention of Cancer Trial of adult participants indicated that supplementation with 200 μg per day of Se derived from high-Se yeast for 7.7 years was associated with an elevated risk of self-reported T2DM[25]. Like Cu, it is also important to determine the optimal cutoff points for Se status and intake to mitigate potential adverse effects on glucose metabolism while simultaneously increasing the prevention of T2DM.
The interpretation of the observed elemental differences between pediatric T1DM and T2DM patients should be approached carefully, as the two cohorts differed in several demographic and clinical characteristics. Specifically, participants with T2DM were older, had greater body weight, higher BMI percentiles, and different ethnic distributions compared with participants with T1DM. These factors have independently been associated with alterations in trace element metabolism, inflammatory status, oxidative stress, insulin resistance, and nutritional patterns, all of which may influence circulating metal concentrations. Therefore, the observed differences in serum Zn, Cu, Mg, Co, and other trace elements may reflect not only differences related to diabetes type but also the influence of age, adiposity, metabolic status, and other unmeasured confounders. Although our subgroup analyses by sex and ethnicity provide additional insight into these relationships, future studies employing matched cohorts and multivariable analytical approaches will be required to determine the independent contribution of diabetes type to alterations in elemental profiles.
One of the valuable points of this study is its relatively large, well-characterized cohorts of children and adolescents with both T1DM and T2DM. This allows for a direct comparison of trace element profiles between these clinically distinct groups. Additionally, the study includes multiple common serum minerals and their ratios, along with detailed demographic and metabolic data, which provides a reliable and complete assessment of micronutrient status in pediatric diabetes. However, several limitations should be considered when interpreting the findings of this study. First, the cross-sectional design precludes the determination of causal relationships between trace-element alterations and glycemic control. Second, the absence of a healthy control group limits our ability to determine whether the observed elemental differences represent diabetes-associated abnormalities or differences specific to T1DM and T2DM. Consequently, the observed associations should be interpreted as hypothesis-generating rather than definitive evidence of disease-specific alterations. Third, significant differences in age, BMI, body weight, sex distribution, and diabetes duration were observed between the T1DM and T2DM cohorts, raising the possibility of residual confounding. Fourth, information on dietary intake, micronutrient supplementation, socioeconomic status, physical activity, pubertal stage, and urinary trace-element excretion was unavailable and therefore could not be evaluated. Fifth, although both race and ethnicity data were available in the registry, the present study focused on comparisons between Hispanic and non-Hispanic participants because this classification was consistently available across the cohort and represented the primary ethnicity variable collected by the PDC. Consequently, potential differences among specific racial groups, including White and Black/African American participants, were not comprehensively evaluated. Future studies with larger, more diverse cohorts should investigate race- and ethnicity-specific elemental patterns and their relationships with glycemic control in pediatric diabetes. Sixth, although the statistical methods used were appropriate for the predefined pairwise comparisons performed in this study, multivariable analytical approaches may provide a more comprehensive assessment of the independent and interactive effects of demographic and clinical variables on elemental profiles. Seventh, children and adolescents were analyzed as a single pediatric cohort. Because developmental stage and pubertal maturation may influence mineral metabolism and glycemic regulation, age-stratified and pubertal-stage-specific analyses should be performed in future studies when such data are available. Eighth, an additional limitation of this study is that, although the overall cohort size was relatively large, dividing by sex and ethnicity resulted in smaller subgroup sample sizes. This may have reduced statistical power to detect subtle differences. Therefore, the subgroup analyses should be considered exploratory and hypothesis-generating, and should be validated in larger, independent cohorts. Ultimately, the higher prevalence of Hispanic and Black/African American participants in the T2DM cohort may be influenced by unmeasured social determinants of health, including socioeconomic status, healthcare access, dietary patterns, environmental exposures, and other contextual factors that were not available in the current dataset. Therefore, the observed demographic differences should not be interpreted solely as biological associations.
CONCLUSION
This study revealed that children and adolescents with T1DM and T2DM exhibit distinct serum elemental profiles. Significant differences were found in the serum concentrations of Mg, Cu, Zn, Zn/Fe ratio, Co, and Sb. Multiple elements and elemental ratios, including Cu, Zn, Zn/Fe, and Zn/Cu, were associated with HbA1c levels. This suggests that imbalances in these elements may contribute to glycemic regulation and the pathophysiology of diabetes in pediatric patients. Differences in elemental profiles among individuals by sex and ethnicity provide valuable interpretations, particularly for essential minerals such as Cu, Zn, and Zn/Cu ratio. In those with T2DM, sex- and ethnicity-specific variations in Cu and Zn levels and their ratio revealed how demographic factors may influence elemental metabolism. Furthermore, for individuals with T1DM, it is remarkable that ethnicity influences serum levels of Na, Cu, and the Zn/Cu ratio, which suggests that diverse biological and cultural backgrounds can play a critical role in nutritional and metabolic health. Regarding the Zn/Cu ratio, it did not differ significantly between T1DM and T2DM; therefore, this finding should be interpreted with caution and not as a discriminatory marker between diabetes types. Nevertheless, the Zn/Cu ratio demonstrated significant inverse associations with HbA1c in both T1DM and T2DM, suggesting a potential relationship with glycemic regulation rather than diabetes classification. These findings may also expand our understanding of the relationship between elemental homeostasis and glycemic control in pediatric diabetes. Further longitudinal studies with larger, more diverse cohorts that include healthy control groups are needed to validate these results and clarify their clinical significance.
Lawrence JM, Divers J, Isom S, Saydah S, Imperatore G, Pihoker C, Marcovina SM, Mayer-Davis EJ, Hamman RF, Dolan L, Dabelea D, Pettitt DJ, Liese AD; SEARCH for Diabetes in Youth Study Group. Trends in Prevalence of Type 1 and Type 2 Diabetes in Children and Adolescents in the US, 2001-2017.JAMA. 2021;326:717-727.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 551][Cited by in RCA: 474][Article Influence: 94.8][Reference Citation Analysis (5)]
Dabelea D, Mayer-Davis EJ, Saydah S, Imperatore G, Linder B, Divers J, Bell R, Badaru A, Talton JW, Crume T, Liese AD, Merchant AT, Lawrence JM, Reynolds K, Dolan L, Liu LL, Hamman RF; SEARCH for Diabetes in Youth Study. Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009.JAMA. 2014;311:1778-1786.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 1182][Cited by in RCA: 1034][Article Influence: 86.2][Reference Citation Analysis (5)]
Fukunaka A, Fujitani Y.
Role of Zinc Homeostasis in the Pathophysiology of Diabetes. In: Yasui H, Kambe T, editors. Zinc in Biology: Molecular Structures, Cellular Processes and Living Systems. Royal Society of Chemistry, 2025: 214-228.
[PubMed] [DOI]
Navarro-Alarcón M, López-G de la Serrana H, Pérez-Valero V, López-Martínez C. Serum and urine selenium concentrations as indicators of body status in patients with diabetes mellitus.Sci Total Environ. 1999;228:79-85.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 71][Reference Citation Analysis (0)]
Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, Wei R, Curtin LR, Roche AF, Johnson CL. 2000 CDC Growth Charts for the United States: methods and development.Vital Health Stat 11. 2002;1-190.
[PubMed] [DOI]
Huang R, Kong X, Geng R, Wu J, Li J, Gu Y, Wu Y, You D, Zhao Y, Ni S, Zhong Z, Bai J. Associations of dietary magnesium intake with the risk of atherosclerotic cardiovascular disease and mortality in individuals with and without type 2 diabetes: A prospective study in the UK Biobank.Diabetes Metab. 2024;50:101554.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 3][Cited by in RCA: 3][Article Influence: 1.5][Reference Citation Analysis (0)]
Maher MM, Helal SR. A Study of Serum Magnesium, Zinc, Copper and Glycohemoglobin In Children With Type 1 Diabetes Mellitus.Alex J Pediatr. 2002;16:285-289.
[PubMed] [DOI]
Aly HF, Mantawy MM. Comparative effects of zinc, selenium and vitamin E or their combination on carbohydrate metabolizing enzymes and oxidative stress in streptozotocin induced-diabetic rats.Eur Rev Med Pharmacol Sci. 2012;16:66-78.
[PubMed] [DOI]
Estakhri M, Djazayery A, Eshraghian M, Majdzadeh R, Jalali M, Karamizadeh Z, Chamari M, Milani MP. Serum zinc levels in children and adolescents with type-1 diabetes mellitus.Iran J Public Health. 2011;40:83-88.
[PubMed] [DOI]
Takao T, Yanagisawa H, Suka M, Yoshida Y, Onishi Y, Tahara T, Kikuchi T, Kushiyama A, Anai M, Takahashi K, Wakabayashi Sugawa S, Yamazaki H, Kawazu S, Iwamoto Y, Noda M, Kasuga M. Synergistic association of the copper/zinc ratio under inflammatory conditions with diabetic kidney disease in patients with type 2 diabetes: The Asahi Diabetes Complications Study.J Diabetes Investig. 2022;13:299-307.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 19][Cited by in RCA: 24][Article Influence: 6.0][Reference Citation Analysis (0)]
P-Reviewer: Akopova OV, PhD, Principal Investigator, Senior Scientist, Ukraine; Soliman HMH, Lecturer, Post Doctoral Researcher, Egypt; Xin YJ, Assistant Professor, PhD, China S-Editor: Fan M L-Editor: A P-Editor: Wang CH
