Type 1 Diabetes
Metal Homeostasis Copper dysregulation plays a definitive role in the pathogenesis of Type 1 Diabetes Mellitus (DM). Elevated copper levels increase the risk of developing DM by 15-fold per standard deviation, highlighting copper’s critical influence on oxidative stress and inflammatory pathways central to the disease. Studies show that DM patients exhibit higher copper levels and […]
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
Overview 
Interventions 
References Overview
Metal Homeostasis
Copper dysregulation plays a definitive role in the pathogenesis of Type 1 Diabetes Mellitus (T1DM). Elevated copper levels increase the risk of developing T1DM by 15-fold per standard deviation, highlighting copper’s critical influence on oxidative stress and inflammatory pathways central to the disease. Studies show that T1DM patients exhibit higher copper levels and copper-to-zinc ratios, alongside decreased zinc and magnesium, correlating directly with poorer glycemic control and increased disease severity. These findings establish copper homeostasis as a pivotal factor in T1DM progression, underscoring its potential as a biomarker and therapeutic target. [1]
Interventions
Copper chelators such as tetrathiomolybdate (TM) and triethylenetetramine (TETA) have shown promise as microbiome-targeted interventions (MBTIs) for Type 1 Diabetes Mellitus (T1DM) by addressing copper dysregulation and its downstream effects, including oxidative stress, inflammation, and metabolic imbalances. TM effectively reduced serum copper levels, improved insulin sensitivity, and modulated glucose tolerance in diabetic models,[2]while TETA mitigated T1DM complications, such as albuminuria and kidney fibrosis.[3] Our validation process aligns these therapeutic effects with microbial imbalances, oxidative stress regulation, and key pathological markers of T1DM, ensuring interventions address dysbiosis and the condition’s core biological mechanisms. Promising candidates with partial alignment or preliminary benefits, like these chelators, are prioritized for further research, advancing innovative therapies for future validation.
| Intervention | Classification | MBTI Status |
|---|---|---|
| Tetrathiomolybdate (TM) | Pharmaceutical | Promising Candidate |
| Triethylenetetramine (TETA) | Pharmaceutical | Promising Candidate |
Zinc
Zinc is an essential trace element vital for cellular functions and microbiome health. It influences immune regulation, pathogen virulence, and disease progression in conditions like IBS and breast cancer. Pathogens exploit zinc for survival, while therapeutic zinc chelation can suppress virulence, rebalance the microbiome, and offer potential treatments for inflammatory and degenerative diseases.
Microbiome-Targeted Interventions (MBTIs)
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.
References
- Potential Role of Copper in Diabetes and Diabetic Kidney Disease.. Gembillo G, Labbozzetta V, Giuffrida AE, Peritore L, Calabrese V, Spinella C, Stancanelli MR, Spallino E, Visconti L, Santoro D.. (Metabolites. Dec 22, 2022)
- Role of copper ion in the pathogenesis of type 2 diabetes.. Tanaka A, Kaneto H, Miyatsuka T, Yamamoto K, Yoshiuchi K, Yamasaki Y, Shimomura I, Matsuoka TA, Matsuhisa M.. (Endocr J. 2009)
- Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal-targeted treatments.. Lu J, Gong D, Choong SY, Xu H, Chan YK, Chen X, Fitzpatrick S, Glyn-Jones S, Zhang S, Nakamura T, Ruggiero K, Obolonkin V, Poppitt SD, Phillips AR, Cooper GJ.. (Diabetologia. Jun 11, 2010.)
Gembillo G, Labbozzetta V, Giuffrida AE, Peritore L, Calabrese V, Spinella C, Stancanelli MR, Spallino E, Visconti L, Santoro D.
Potential Role of Copper in Diabetes and Diabetic Kidney Disease.Metabolites. Dec 22, 2022
Tanaka A, Kaneto H, Miyatsuka T, Yamamoto K, Yoshiuchi K, Yamasaki Y, Shimomura I, Matsuoka TA, Matsuhisa M.
Role of copper ion in the pathogenesis of type 2 diabetes.Endocr J. 2009
Lu J, Gong D, Choong SY, Xu H, Chan YK, Chen X, Fitzpatrick S, Glyn-Jones S, Zhang S, Nakamura T, Ruggiero K, Obolonkin V, Poppitt SD, Phillips AR, Cooper GJ.
Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal-targeted treatments.Diabetologia. Jun 11, 2010.