High hemoglobin A1c levels within the non‐diabetic range are associated with the risk of all cancers

Abstract

Previous studies have reported associations between diabetes and cancer risk. However, specific association of hemoglobin A1c (HbA1c) levels with cancer risk remains inconclusive. We followed 29,629 individuals (11,336 men; 18,293 women) aged 46–80 years who participated in the Japan Public Health Center‐based prospective study who had HbA1c measurements available and were cancer‐free at baseline. Cancer incidence was assessed by systemic surveys. We estimated hazard ratios (HRs) for cancer risk with adjustment for age sex, geographic area, body mass index, smoking status, physical activity, alcohol, coffee, vegetable and total energy consumption, and history of cardiovascular disease. After a median follow‐up of 8.5 years, 1,955 individuals had developed cancer. Higher HbA1c levels within both the non‐diabetic and diabetic ranges in individuals without known diabetes were associated with overall cancer risk. Compared with individuals without known diabetes and HbA1c levels of 5.0–5.4%, the HRs for all cancers were 1.27 (95% confidence interval, 1.07–1.52); 1.01 (0.90–1.14); 1.28 (1.09–1.49); and 1.43 (1.14–1.80) for individuals without known diabetes and HbA1c levels <5.0%, 5.5–5.9%, 6.0–6.4%, and ≥6.5%, respectively, and 1.23 (1.02–1.47) for individuals with known diabetes. The lowest HbA1c group had the highest risk of liver cancer, and HbA1c levels were linearly associated with the risk of all cancers after excluding liver cancer (P for linear trend, 0.004). In conclusion, our findings corroborate the notion that glycemic control in individuals with high HbA1c levels may be important not only to prevent diabetes but also to prevent cancer.

Plasma C‐peptide and glycated albumin and subsequent risk of cancer: From a large prospective case‐cohort study in Japan

“…3 cups/day) and family history of cancer. 5 In addition to HR2 in men and women combined and in men, HR3 was further adjusted for C-peptide or glycated albumin. 6 In addition to HR1 in women, HR2 was further adjusted for BMI (<21, 21-< 25, 25-< 30, or !…”

“…4 Further adjusted for sex. 5 In addition to HR1 in men and women combined and in men, HR2 was further adjusted for BMI (<21, 21-< 25, 25-< 30, or ! 30 kg/m 2 ), smoking (never, pack-years of ever or current smokers: <20, 20-< 40, or !…”

“…1 Further, recent prospective studies have associated the higher levels of blood glucose which underlie the pathophysiology of DM with increased risk of cancer. [2][3][4][5] Nevertheless, it is possible that DM-related carcinogenesis cannot be explained by the influence of higher blood glucose levels only. Before developing DM, many subjects are likely to have higher levels of insulin to maintain physiological levels of blood glucose.…”

Diabetes and cancer risk: A Mendelian randomization study

“…Over the decades, a number of cohort studies reported associations between type 2 diabetes and increased cancer risks, especially liver, colorectal and pancreatic cancers . More recently, studies have shown that high levels of blood glucose or glycated hemoglobin A1c are associated with cancer incidence. These associations are biologically plausible, given that hyperglycemia increases mitochondrial glucose oxidation, thereby promoting DNA damage through oxidative stress.…”

Hyperinsulinemia and Insulin Resistance: Scope of the Problem

“…49,50 Even within the normal range, HbA1c is positively correlated to an increased risk for all cancers (excluding that of the liver), which mirrors the increased risk for CVD. 51 Metabolic syndrome, IR and hyperglycaemia are all associated with breast cancer recurrence, which has many oncologists and dietitians calling current dietary guidelines into question. 52 AD is now frequently referred to as 'diabetes of the brain' or 'type 3 diabetes', bringing immediate attention to the role of insulin dysregulation and impaired blood glucose.…”