Hypoinsulinemia and Malignancy Risk
No, hypoinsulinemia (low insulin levels) is not associated with increased cancer risk; rather, the opposite is true—hyperinsulinemia (elevated insulin levels) is consistently linked to increased cancer development, progression, and mortality.
The Evidence Points to Hyperinsulinemia, Not Hypoinsulinemia, as the Concern
The available evidence uniformly demonstrates that elevated insulin levels, not low insulin levels, pose cancer-related concerns:
Hyperinsulinemia and Cancer Outcomes
Hyperinsulinemia is associated with 2-3 fold increased risk of cancer recurrence and death in patients with early-stage breast cancer, with those in the highest quartile of fasting insulin levels showing significantly worse outcomes compared to those with the lowest levels 1.
Patients with colorectal cancer in the highest quartile of C-peptide (a marker of insulin production) at diagnosis demonstrate higher overall mortality compared to those with lower levels 1.
Insulin resistance and accompanying hyperinsulinemia are implicated in tumor initiation and progression through multiple mechanisms including increased bioavailable IGF-1, altered sex hormone metabolism, increased reactive oxygen species production, and promotion of a pro-inflammatory environment 2, 3, 4.
Metabolic Context in Cancer Patients
Cancer patients typically exhibit insulin resistance with relatively elevated insulin levels, not hypoinsulinemia 1:
The insulin-to-cortisol ratio is commonly reduced in cancer patients due to increased cortisol secretion, but this reflects altered hormonal balance rather than absolute hypoinsulinemia 1.
Cancer cachexia is characterized by impaired glucose tolerance due to insulin resistance, increased glucose turnover, and enhanced gluconeogenesis—all occurring in the context of adequate or elevated insulin levels 1.
Clinical Implications
From a cancer risk perspective, lower insulin levels are protective, not harmful. The clinical focus should be on:
Avoiding hyperinsulinemia through weight management, physical activity, and appropriate diabetes management in cancer survivors 1.
Recognizing that interventions promoting insulin sensitivity may reduce cancer risk and improve outcomes 2, 3, 4.
Important Caveat: Insulinomas
The only malignancy-related scenario involving true hypoinsulinemia concerns insulinomas—neuroendocrine tumors that paradoxically cause hypoglycemia through inappropriate insulin secretion 1. However, these tumors are characterized by elevated, not low, insulin levels relative to glucose (insulin >3-6 mcIU/mL when glucose <40-45 mg/dL), and 90% pursue an indolent course curable with surgery 1.