Glycated hemoglobin and cancer incidence and mortality in the Atherosclerosis in Communities (ARIC) Study, 1990–2006

Abstract

Diabetes is a risk factor for many cancers; chronic hyperglycemia is hypothesized to be, in part, explanatory. We evaluated the association between glycated hemoglobin, a time-integrated glycemia measure, and cancer incidence and mortality in non-diabetic and diabetic men and women. We conducted a prospective study of 12,792 cancer-free participants attending the second visit (1990–1992) of the Atherosclerosis Risk in Communities (ARIC) Study. We measured glycated hemoglobin in whole-blood samples using HPLC. Incident cancers were ascertained from registries and hospital records through 2006. We estimated multivariable-adjusted hazard ratios (HR) of cancer incidence and mortality for non-diabetic participants with values ≥5.7% (elevated), non-diabetic participants with <5.0% (low), and diabetic participants all compared with non-diabetic participants with 5.0–5.6% (normal). We ascertained 2,349 incident cancer cases and 887 cancer deaths. Compared with non-diabetic women with normal glycated hemoglobin, non-diabetic women with elevated values had an increased risk of cancer incidence (HR:1.24; 95% CI:1.07,1.44) and mortality (HR:1.58; 95% CI:1.23,2.05) as did diabetic women (incidence, HR:1.30; 95% CI:1.06,1.60, mortality, HR:1.96; 95% CI:1.40,2.76). Non-diabetic women with low values also had increased risk. Diabetic women with good glycemic control (<7.0%) had a lower cancer risk than those with higher values. Glycated hemoglobin in non-diabetic and diabetic men, and diabetes were not statistically significantly associated with total cancer risk. Our findings support the hypothesis that chronic hyperglycemia, even in the non-diabetic range, increases cancer risk in women. Maintaining normal glycated hemoglobin overall, and good glycemic control among diabetic adults, may reduce the burden of cancer, especially in women.

Diabetes and Risk of Cancer

“…Most recent study conducted on 12,792 participants categorized in relation to HbA 1c levels, with median 15-year followup, published similar finding [29]. Nondiabetic women with elevated HbA 1c values (≥5.7%) had an increased risk of cancer incidence (HR 1.24; 95% CI; 1.07–1.44) and so did diabetic women (HbA 1c > 6.5%) with HR 1.30 (95% CI; 1.06–1.60).…”

Does cancer risk increase with HbA1c, independent of diabetes?

“…The RCS model obtained from these studies was statistically significant ( P non-linearity =0.0353, P heterogeneity =0.1537, I 2 =40.1%), with increasing risk at lower HbA 1c levels, and decreasing risk at higher HbA 1c levels. Neither the increasing log-linear HR mortality model ( P =0.1573), nor the increasing-decreasing RCS HR mortality model from the Joshu et al (2012) study was statistically significant ( P non-linearity =0.2996).…”

Correlations of microRNA-124a and microRNA-30d with clinicopathological features of breast cancer patients with type 2 diabetes mellitus

“…Additionally, HbA1c may capture the glucose exposure that may relevant to cancer risk and higher HbA1c level may be correlated with a higher risk of cancer incidence and cancer-related mortality (Joshu et al 2012; Li et al 2014). Estrogen has also been reported to be involved in the pathogenesis and disease progression of BC and down-regulated estrogen level could be a potential management for most patients with estrogen responsive tumors (Su et al 2013).…”