Risk of Endometrial Cancer and Diabetes Mellitus Type 2

A meta-analysis based on 16 studies (3 cohort and 13 case-cohort studies) showed for
12 studies a statistically significantly increased risk and for 4 studies a non-significant increased risk of endometrial cancer [24]. The association between diabetes and incidence of endometrial cancer and the potential effect of modification by obesity and physical activity was prospectively examined in the Swedish Mammography Cohort

Study. Diabetes was associated with a twofold increased risk, and combination of diabetes with obesity and low physical activity was associated with a further increased risk for endometrial cancer [25]. Therefore, interventions to reduce body weight and increase physical activity may have important implications in terms of endometrial cancer and future management of diabetic subjects.
In 1986, Folsam et al. [26] obtained risk factor information on 41,836 women aged
55–66 years living in Iowa. They followed those initially free of cancer through to 2000 and identified incident endometrial cancers via linkage to a cancer registry. Diabetes was associated with poorer survival after incident endometrial cancer, independent of tumor stage and grade. The findings support the possibility of a diabetes-related condition, such as hyperglycemia or hyperinsulinemia, contributing to poorer endometrial cancer survival. A case-control study, which was nested within three cohorts in New York (USA), Umeå (Sweden) and Milan (Italy), investigated for the first time prospectively
the association of prediagnostic blood concentrations of C-peptide, a marker of
pancreatic insulin production, IGF-1, (insulin-like growth factor binding protein,
IGFBP) IGFBP-1, -2 and -3 with endometrial cancer risk. Chronic hyperinsulinemia, as
reflected by increased circulating C-peptide, was associated with increased endometrial cancer risk. Risk was unrelated to levels of IGF-1, IGFBP-2 and IGFBP-3 [27].
A German study (charts abstracted from patients with endometrial cancer from
1985 to 1995) investigating the influence of diabetes mellitus type 2 and nodal distribution in endometrial cancer showed a univariate correlation between lymph node
involvement and diabetes [28]. The extension of this study to the year 2003 revealed
by multivariate analysis that diabetes mellitus type 2, FIGO stage and depth of
myometrial invasion were significantly associated with overall survival [29].
A case-control study performed in Italy and Switzerland found a supramultiplicative
effect for obese diabetic women and risk of endometrial cancer [30]. Obesity is a
well-known risk factor for the development of endometrial cancer, however weight
alone does not account for all cases. Insulin resistance also contributes to an increased risk for endometrial cancer. Adiponectin is a protein secreted by adipose cells and has been shown to be a surrogate marker for insulin resistance, with low levels of adiponectin correlated with hyperinsulinemia and a degree of insulin resistance.

Indeed, women with endometrial cancer were more likely to have low adiponectin
levels than controls, even after adjusting for body mass index. This suggests that
insulin resistance is independently associated with endometrial cancer [31] and
insulin resistance/hyperinsulinemia is associated with poorly differentiated endometrial adenocarcinomas and a more aggressive course of the disease [32].