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Review
. 2024 Apr 9;13(8):663.
doi: 10.3390/cells13080663.

Metabolic Alteration Bridging the Prediabetic State and Colorectal Cancer

Antonino Colloca  1 , Isabella Donisi  1 , Camilla Anastasio  1 , Maria Luisa Balestrieri  1 , Nunzia D'Onofrio  1
Affiliations
Review

Metabolic Alteration Bridging the Prediabetic State and Colorectal Cancer

Antonino Colloca et al. Cells. .

Abstract

Prediabetes and colorectal cancer (CRC) represent compelling health burdens responsible for high mortality and morbidity rates, sharing several modifiable risk factors. It has been hypothesized that metabolic abnormalities linking prediabetes and CRC are hyperglycemia, hyperinsulinemia, and adipokines imbalance. The chronic stimulation related to these metabolic signatures can favor CRC onset and development, as well as negatively influence CRC prognosis. To date, the growing burden of prediabetes and CRC has generated a global interest in defining their epidemiological and molecular relationships. Therefore, a deeper knowledge of the metabolic impairment determinants is compelling to identify the pathological mechanisms promoting the onset of prediabetes and CRC. In this scenario, this review aims to provide a comprehensive overview on the metabolic alterations of prediabetes and CRC as well as an overview of recent preventive and therapeutic approaches for both diseases, focusing on the role of the metabolic state as a pivotal contributor to consider for the development of future preventive and therapeutic strategies.

Keywords: chronic inflammation; colorectal cancer; hormone dysregulation; metabolic alteration; microbiota; nutrition; obesity; pharmacotherapy; physical activity; prediabetes.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Risk factors and determinants in prediabetes pathogenesis. The interplay among different factors, including oxidative stress and inflammation, unhealthy lifestyle habits, hormonal dysregulation, and microbiota alterations, results in the aberrant activation of different metabolic pathways contributing to the pathogenesis of prediabetes.
Figure 2
Figure 2
Prediabetes as an independent risk and prognostic factor in CRC. Schematic representation of typical prediabetes alterations and their molecular interplay as a trigger for CRC onset and development. PPAR-γ, peroxisome proliferator-activated receptor gamma; SREBP1 sterol regulatory element-binding transcription factor 1; IR, insulin receptor; IGF-1R, insulin-like growth factor 1 receptor; Akt, protein kinase B.
Figure 3
Figure 3
Common therapeutic strategies in prediabetes and CRC. A balanced nutritional plan rich in bioactive molecules accompanied by regular exercise sessions represents an effective approach against prediabetes and CRC. The off-label administration of antidiabetic drugs, such as metformin, GLP1 receptor agonists, and SGLT2 inhibitors, might also be effective in the prevention and treatment of both diseases. GLP1, glucagon-like peptide 1; SGLT2, sodium-glucose co-transporter 2.
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