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 nondiabetic 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 nondiabetic participants with values ≥ 5.7% (elevated), nondiabetic participants with <5.0% (low) and diabetic participants all compared with nondiabetic participants with 5.0-5.6% (normal). We ascertained 2,349 incident cancer cases and 887 cancer deaths. Compared with nondiabetic women with normal glycated hemoglobin, nondiabetic 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). Nondiabetic 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 nondiabetic 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 nondiabetic 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.

Figure 1. Multivariable-adjusted hazard ratio of cancer incidence and glycated hemoglobin using restricted quadratic splines with knots at the 10th, 50th, and 90th percentiles

Gray shading represents 95% confidence interval; background histogram, distribution of glycated hemoglobin in the sub-population. All models adjusted for age (continuous) at the second visit, race/ethnicity (white, black), ARIC study site, education level (less than high school, high school/equivalent, college or above), cigarette smoking status (never, former, current), cigarette-years smoked (continuous), body mass index (continuous), and waist circumference (continuous). A: Among non-diabetic women; 5.0% reference; also adjusted for post-menopausal hormone use (no, yes). B: Among non-diabetic men; 5.0% reference. C: Among diabetic women; 7.0% reference; also adjusted for post-menopausal hormone use. D: Among diabetic men; 7.0% reference.

Figure 2. Multivariable-adjusted hazard ratio of cancer mortality and glycated hemoglobin using restricted quadratic splines with knots at the 10th, 50th, and 90th percentiles

Gray shading represents 95% confidence interval; background histogram, distribution of glycated hemoglobin in the sub-population. All models adjusted for age (continuous) at the second visit, race/ethnicity (white, black), ARIC study site, education level (less than high school, high school/equivalent, college or above), cigarette smoking status (never, former, current), cigarette-years smoked (continuous), body mass index (continuous), and waist circumference (continuous). A: Among non-diabetic women; 5.0% reference; also adjusted for post-menopausal hormone use (no, yes). B: Among non-diabetic men; 5.0% reference. C: Among diabetic women; 7.0% reference; also adjusted for post-menopausal hormone use. D: Among diabetic men; 7.0% reference.