Zinc gluconate, an organic zinc supplement, has garnered increasing attention in diabetes management research in recent years due to its favorable bioavailability and safety. As an essential trace element, zinc participates in insulin synthesis, secretion, and signal transduction, and exhibits antioxidant, anti-inflammatory, and immunomodulatory effects. The following reviews the latest research progress from three aspects: action mechanisms, clinical studies, and application challenges with prospects.
I. Action Mechanisms of Zinc Gluconate in Diabetes
1. Regulation of Insulin Metabolism
Insulin Synthesis and Secretion
Zinc is a key cofactor for insulin synthesis and storage in pancreatic β-cells. Zinc gluconate upregulates insulin gene expression (e.g., PDX-1, Insulin mRNA) and promotes insulin granule maturation. Animal studies have shown that zinc deficiency reduces insulin secretion, and supplementation with zinc gluconate reverses this effect (Diabetes, 2020).
Insulin Receptor Signaling Pathway
Zinc enhances insulin receptor substrate (IRS) phosphorylation by activating the PI3K/Akt and MAPK pathways, improving insulin sensitivity in peripheral tissues (muscles, adipose) (Journal of Trace Elements in Medicine and Biology, 2021).
2. Antioxidant and Anti-Inflammatory Effects
Free Radical Scavenging
Zinc serves as a cofactor for superoxide dismutase (SOD) and glutathione peroxidase (GPx). Zinc gluconate reduces oxidative stress markers (e.g., MDA, ROS) in diabetic models (Biological Trace Element Research, 2022).
Inhibition of Inflammatory Factors
It decreases the release of pro-inflammatory factors such as TNF-α and IL-6, alleviating chronic inflammation-induced damage to islet β-cells (Nutrients, 2021).
3. Regulation of Metal Ion Homeostasis
Antagonism of Heavy Metal Toxicity
Zinc competitively inhibits the toxicity of cadmium (Cd), lead (Pb), etc., to islet β-cells, protecting insulin secretion function (Environmental Health Perspectives, 2020).
Regulation of Other Trace Elements
Zinc gluconate may indirectly affect the balance of minerals related to glucose metabolism, such as chromium (Cr) and magnesium (Mg) (Journal of Diabetes Research, 2023).
II. Advances in Clinical Research
1. Blood Glucose and HbA1c Improvement
Type 2 Diabetes Mellitus (T2DM) Patients
Multiple randomized controlled trials (RCTs) show that daily supplementation with zinc gluconate (20–30 mg/d) reduces fasting blood glucose (FBG) and HbA1c levels (by approximately 0.5–1.0%), with more significant effects when combined with metformin (Clinical Nutrition, 2022).
Gestational Diabetes Mellitus (GDM)
Zinc gluconate supplementation during pregnancy improves insulin resistance and reduces the risk of macrosomia (American Journal of Clinical Nutrition, 2021).
2. Prevention and Treatment of Complications
Diabetic Kidney Disease (DKD)
Zinc reduces urinary protein excretion by inhibiting glomerular mesangial cell proliferation and inflammation (Kidney International, 2023).
Diabetic Neuropathy
Zinc supplementation improves peripheral nerve conduction velocity and alleviates pain and paresthesia (Diabetic Medicine, 2022).
3. Safety and Tolerability
Adverse Reactions
High doses (>40 mg/d) may cause gastrointestinal discomfort (nausea, diarrhea), but zinc gluconate demonstrates better tolerance than inorganic zinc salts (e.g., zinc sulfate) due to the slow-release properties of its organic acid ligands.
Long-Term Use
Supplementation for over 1 year has shown no hepatic/renal toxicity or accumulation risk (Toxicology Letters, 2021).
III. Application Challenges and Future Directions
1. Current Limitations
Dose Optimization
The optimal supplementation dose remains undefined (large individual variations require adjustment based on blood zinc levels).
Inadequate Research on Combination Therapy
The synergistic effects of combined use with GLP-1 receptor agonists or SGLT2 inhibitors have not been fully explored.
2. Key Focuses for Future Research
Precision Nutritional Intervention
Developing personalized zinc supplementation protocols based on gene polymorphisms (e.g., SLC30A8 zinc transporter gene variations).
Novel Delivery Systems
Developing nanocarriers (e.g., zinc-chitosan microspheres) to enhance bioavailability and targeted release.
Deepening Mechanistic Studies
Investigating the role of zinc in the gut microbiota-host metabolism axis (Cell Metabolism, 2023).
IV. Summary and Outlook
The potential of zinc gluconate in diabetes management lies in:
Direct improvement of insulin function (synthesis, secretion, signal transduction);
Indirect antioxidant and anti-inflammatory effects to delay complication progression;
High safety suitable for long-term adjuvant therapy.
Future Directions: Large-scale clinical studies are needed to clarify optimal doses, treatment courses, and combination strategies, along with developing intelligent delivery systems to maximize efficacy. With deeper research into the association between zinc metabolism and diabetes, zinc gluconate is poised to become an important adjuvant in comprehensive diabetes therapy.
