Leukemia Survival Likely Not Affected by Diabetes, Hemoglobin A1C

Research findings from Mayo Clinic investigators in Arizona demonstrate that diabetes did not increase the risk of death among patients with acute (AML) or chronic myeloid leukemia (CML), according to the study published in Future Science OA.

Nor did leukemia status have an impact on glycemic control for these patients, in this retrospective study that saw patients with (n = 70) and without diabetes (n = 70; the control cohort), matched 1:1, who were seen between January 1, 2007, and December 31, 2015. Electronic health records were reviewed for overlaps of cancer diagnoses and diabetes claims.

The primary outcome was overall survival (OS), defined as “time from leukemia diagnosis until death of any cause,” with a secondary outcome of glucose level at 1 year after leukemia diagnosis. Median patient age was 62 (range, 19-94), most were men (60%) and non-Hispanic (60%) or White (83.6%), and 88.6% had AML.

“Studies have shown an increased risk of death of certain solid cancers in patients with diabetes, but data are limited and inconsistent regarding the association between leukemia, diabetes, and death,” the authors noted. “The goal of this study was to evaluate the association between diabetes and survival among patients with acute and chronic myeloid leukemia and the association between leukemia and glycemic control.”

Results show that close to 36% (n = 25) of patients in the diabetes cohort had a mean (SD) hemoglobin A1C of 6.8% (1.3%) with 1 year of follow-up of diagnosis—which did not change. Mean glucose values did significantly differ, though, between the groups (P < .001).

Three-year OS rates were almost equal, however, in the diabetes and control cohorts, at 46% (95% CI, 35%-61%) and 45% (95% CI, 33%-61%; P = .79), respectively. This was despite graft-versus-host disease occurring at similar rates in both cohorts (P < .001), close to 80% of all patients undergoing chemotherapy, and 16% of the control cohort and 21% of the diabetes cohort receiving targeted therapy.

A prominent factor related to potential cancer development from the presence of diabetes is the disturbance of glucose metabolism, which can lead to the increased uptake of glucose by cancer cells, which itself provides a mechanism of growth for those malignant cells.

Analyses further revealed the following:

• An OS HR of 1.05 (95% CI, 0.57-1.94; P = .88) for 3 years for the matched pairs
• A relapse-free survival (RFS) HR of 1.10 (95% CI, 0.61-1.98; P = .76)
• Higher 3-year RFS rate in the nondiabetes cohort:
  • Nondiabetes group: 43% (95% CI, 32%-59%)
  • Diabetes group: 34% (95% CI, 23%-49%)
• Patients who had comorbid AML and diabetes vs those without diabetes had higher rates of variations/translocations: 81% vs 46% (P = .001)

The authors highlight 2 possible reasons for their positive findings:

1. First-line treatment of diabetes with metformin, which previous studies have shown to have protective anticancer effects
2. Insulin use during leukemia treatment, which was shown in mouse models to decrease insulin-like growth factor binding protein 1 levels, thereby decreasing insulin resistance

“There are limited studies addressing long-term outcomes in patients with leukemia and diabetes; confirmation of these observations in larger patient cohorts is needed,” the authors concluded. “Investigation of the effect of intensive insulin therapy on leukemia survival rate is of interest and worthy of future study.”

Also, because most of the patients in the diabetes cohort lacked data on hemoglobin A1C levels, further study and quality-improvement initiatives are needed in this area.

Reference

Wiedmeier J, Mountjoy LJ, Buras MR, et al. Mortality and glycemic control among patients with acute and chronic myeloid leukemia and diabetes: a case-control study. Future Sci OA. Published online October 26, 2020. doi:10.2411/fsoa-2020-0177