Insulin Resistance Amplifies Risk of Colorectal Cancer Development

Chong-Chi Chiu, MD

Credit: ResearchGate

A new investigation exploring the correlation of insulin resistance with type 2 diabetes (T2D), obesity, and colorectal cancer (CRC) occurrence found elevated blood insulin levels and insulin resistance each contributed to a higher CRC risk.¹

These data, presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC) in Los Angeles, California, identified higher levels of insulin and resistin in patients with CRC, which remained after performing adjustments for relevant patient factors.

“Obesity appeared to exacerbate higher blood insulin levels, insulin resistance, along with resultant hyperinsulinemia and elevated blood sugar levels, significantly heightens the risk of developing CRC,” wrote the investigative team, led by Chong-Chi Chiu, MD and Chao-Ming Hung, MD, PhD, department of general surgery, E-Da Cancer Hospital.

Obesity has been closely linked to insulin resistance and low-grade inflammation, with increased evidence tying insulin resistance to the connection between obesity and CRC.² The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index is used by clinicians to assess hyperinsulinemia and early insulin resistance stages.

Resistin, a hormone that plays a critical role in inflammation, has also been linked to insulin resistance and obesity.³ However, there is little evidence of the relationship between HOMA-IR and CRC, with several studies reporting a correlation, while others have demonstrated conflicting results.

For this analysis, Chiu and colleagues explored the connection between insulin resistance and obesity, focusing on CRC incidence. The team collected data from the Taiwan Cancer Registry dataset and the Taiwan National Health Insurance Research Database, with enrollment of all patients with CRC and controls between May 2013 and March 2023.

Plasma levels of glucose, insulin, and resistin were measured, while insulin resistance was calculated from the HOMA-IR index. Logistic regression analysis helped adjust for confounding factors, including age, body mass index (BMI), gender, smoking history, and family history of CRC.

Upon analysis, Chiu and colleagues found that patients with CRC exhibited statistically meaningful elevated levels of HOMA-IR, compared with the control cohort (1.7 ± 0.3 vs. 1.2 ± 0.2; P <.001). Stratification of patients with CRC by cancer location identified elevated levels of insulin (6.9 ± 1.2 vs. 6.0 ± 1.1; P = .032) and resistin (6.9 ± 1.3 vs. 6.4 ± 1.4; P = .046), as well as an increased HOMA-IR (1.7 ± 0.2 vs. 1.1 ± 0.1; P <.001) in patients with CRC.

Moreover, resistin levels showed a positive correlation with insulin levels among both patients with CRC (P <.001) and the control cohort (P <.002), independent of both age and BMI. Overall, Chiu and colleagues indicated resistance may contribute to CRC development, given this association with obesity, insulin resistance, and inflammation.

The team further pointed to the role of resistin as an acting mediator between inflammation and cancer, with higher resistin levels correlated with chronic inflammation linked to cancer. They suggested that resistin upregulates pro-inflammatory cytokines, including IL-6 and TNF-α, which could further elevate cancer risk through the NF-kB pathway.

However, Chiu and colleagues admitted the limitations of the study included the modest sample size and lack of data on other hormones linked to obesity, with insulin resistance potentially affecting the results. They noted the study only measured plasma resistin levels, without a concurrent look at genetic or protein variations.

“The study aligns with previous findings showing elevated resistin levels in CRC patients but contrasts with studies that found no association,” Chiu and colleagues added.

References

1. _{Chiu CC, Hung CM, et al. Correlation of insulin resistance, type 2 Diabetes Mellitus, Obesity, and Colorectal Cancer Occurrence. Presented at World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC) 2024. Los Angeles, California. December 12-14, 2024.}
2. _{Shimobayashi M, Albert V, Woelnerhanssen B, et al. Insulin resistance causes inflammation in adipose tissue. J Clin Invest. 2018;128(4):1538-1550. doi:10.1172/JCI96139}
3. _{Deb A, Deshmukh B, Ramteke P, Bhati FK, Bhat MK. Resistin: A journey from metabolism to cancer. Transl Oncol. 2021;14(10):101178. doi:10.1016/j.tranon.2021.101178}