Association between hyperinsulinemia and increased risk of cancer death in nonobese and obese people: A population‐based observational study

Obesity, metabolic syndrome and type 2 diabetes are associated with cancer‐related mortality. We assessed whether hyperinsulinemia is a risk factor for cancer death in nonobese people without diabetes. We conducted a prospective cohort study using data from the National Health and Nutrition Examination Survey 1999–2010 and followed up the participants until December 31, 2011. For the primary analysis of cancer mortality, we used Cox proportional hazard models to estimate hazard ratios (HRs) in the participants with hyperinsulinemia and those without. Hyperinsulinemia was defined as a fasting insulin level of ≥10 μU/mL. To identify causes of deaths, the International Classification of Diseases, Tenth Revision codes were used. This study included 9,778 participants aged 20 years or older without diabetes or a history of cancer: 6,718 nonobese participants (2,057 with hyperinsulinemia [30.6%]) and 3,060 obese participants (2,303 with hyperinsulinemia [75.3%]). A total of 99.9% completed follow‐up. Among all study participants, cancer mortality was significantly higher in those with hyperinsulinemia than in those without hyperinsulinemia (adjusted HR 2.04, 95% CI 1.24–3.34, p = 0.005). Similarly, among nonobese participants, multivariable analysis showed that cancer mortality was significantly higher in those with hyperinsulinemia than in those without (adjusted HR 1.89, 95% CI 1.07–3.35, p = 0.02). Considering that nonobese people with hyperinsulinemia were at higher risk of cancer mortality than those without hyperinsulinemia, improvement of hyperinsulinemia may be an important approach for preventing cancer regardless of the presence or absence of obesity. What's new? Obesity, metabolic syndrome, and type 2 diabetes are associated with cancer‐related mortality, with hyperinsulinemia possibly playing a role. However, hyperinsulinemia also occurs in nonobese people. So far, no study has investigated whether hyperinsulinemia in nonobese people without diabetes is associated with increased risks of cancer‐related death. This prospective cohort study shows that among nonobese people, hyperinsulinemia was associated with a significantly higher risk of cancer mortality. Furthermore, hyperinsulinemia was associated with an increased risk of cancer death in people with normal fasting plasma glucose levels. Improvement of hyperinsulinemia may thus be an important approach for preventing cancer regardless of obesity.