Speakers - 2025 Speakers

Title: Type 1 diabetes mellitus suppresses experimental skin carcinogenesis

Abstract

This study explores the previously uncharted territory of the effects of ultraviolet (UV) radiation on diabetic skin, compared to its well-documented impact on normal skin, particularly focusing on carcinogenesis and aging. Employing hairless SKH-hr2, Type 1(T1D} and Type 2 diabetes was induced by administration of 30 or 20mg/kg streptozocin, respectively, throughout the study and subjected to UV radiation thrice weekly for six months. The investigation included comprehensive assessments of photoaging and photocarcinogenesis in diabetic versus normal skin, Findings reveal that under UV exposure, Type 1 diabetic skin (T1D) showed heightened dehydration, thinning, and signs of accelerated aging. Remarkably, Type 1 diabetic mice did not develop squamous cell carcinoma or pigmented nevi, contrary to normal and Type 2 diabetic skin. Closer examination of metabolic parameters provide a potential mechanism for the refractory response to UV-carcinogenesis in T1D skin. Observations on this study displayed a significant increase in glucose level from 127 mg/dl at base line to 344.14 at one month to 550 at month six; a decrease in Glutathione; and increase in Oxidative Stress (OS) in the Stratum corneum; and reduction in body weight from 29.36 (gr ) compared to 37.99 gr at three months and 24.40 vs 43.86 gr at six months.in the normal control group; and an inhibition of Skin cancer in the T1D group. Recognizing the metabolic complexities in the diabetic phenotype and the link to cancer1, Occam’s Razor might guide us to a solution, i.e., complexity should not be multiplied beyond necessity. OS is elevated due to glutathione decreases related to NADH/NAD+ resulting in depleted fuel (ATP) necessary to carry-on normal growth rates (Caloric restriction, CR) 2,3 leading to extreme un-thriftiness known to inhibit neoplasia (incidence of neoplasia was reduced by 50% in rhesus monkeys). CR may be the mechanism that results in inhibition of skin cancer in T1D.

1 Black, H.S. Oxidative Stress and ROS Link Diabetes and Cancer J. Mol. Pathol. 2024, 5(1), 96-119; https://doi.org/10.3390/jmp5010007

2 Tannenbaum, A. The dependence of the genesis of induced skin tumors on the caloric intake during different stages of carcinogenesis. Cancer Res. 1944, 4; 683-687.

3 Colman, R. J., Anderson, R. M., Johnson, S. C., et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 2009, 325: 201-204. Doi: 10.1126/science. 1173635

  Audience should:

Be informed of the link between Type 1 Diabetes and skin cancer.

Learn of some of the metabolic parameters that are manifested in this link.

Become aware of the potential mechanism by which this link occurs.

Audience take away:

Should consider caloric restriction as a potential mechanism for other metabolic disorders linked to cancer.

It should be useful in both expanding their related research and teaching.

This information may be useful that assists in experimental design for related studies.