In an analysis reported in JAMA Oncology, Zhong and Mao found that a higher daily insulin dose was associated with an increased risk of cancer diagnosis in patients with type 1 diabetes.
Study Details
The analysis used data from the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study to assess risk factors for cancer over a 28-year follow-up. A total of 1,441 patients from 29 centers in North America were enrolled in DCCT between 1983 and 1989; at the end of DCCT in 1993, 1,375 surviving participants continued in the EDIC follow-up study.
By year 18 of EDIC in 2012, 1,303 eligible patients had completed annual cancer history updates, with these patients included in the current analysis. Mean daily insulin doses of < 0.5, ≥ 0.5 to < 0.8, and ≥ 0.8 units/kg were categorized as low, medium, and high.
Key Findings
Among the 1,303 patients in the cohort, 93 (7%) had a cancer diagnosis after a total of 33,813 person-years of follow-up, yielding an incidence rate of 2.8 (95% confidence interval [CI] = 2.2–3.3) per 1,000 person-years.
Among the 93 patients who developed cancer, mean age at diagnosis was 50 years and mean duration of diabetes was 25 years. A total of 57 (61%) were female.
Cancer developed within 10 years of follow-up in 8, between 11 and 20 years in 31, and between 21 and 28 years in 54. The most common diagnoses were skin cancer in 27, breast cancer in 15, reproductive system malignancies in 8, digestive system malignancies in 6, head and neck cancer in 5, bone or blood cancer in 4, and prostate cancer in 4.
In univariate analysis, increasing age and female sex were associated with increased cancer risk. After adjustment for age and sex, greater exercise and higher high-density lipoprotein cholesterol level were associated with decreased risk, and high vs low daily insulin dose was associated with increased risk.
In multivariate analysis, high vs low daily insulin dose was significantly associated with cancer risk (hazard ratio [HR] = 4.13, 95% CI = 1.13–15.17, P = .03). Cancer incidence rates per 1,000 person-years were 2.11, 2.87, and 2.91 in the low-, medium-, and high-dose groups, respectively.
Additional factors associated with cancer risk on multivariate analysis were increasing age (HR per 1-year increase = 1.09, 95% CI = 1.06–1.13, P < .001), female sex (HR = 2.02, 95% CI = 1.28–3.19, P = .003), and moderate/strenuous exercise vs sedentary lifestyle (HR = 0.31, 95% CI = 0.16–0.59, P = .001).
As stated by the investigators, “This study showed that daily insulin dose was associated with cancer risk in [patients with type 1 diabetes]. The risk was significantly higher in the high-dose vs low-dose group… Larger studies in type 1 diabetes are needed to validate this association.”
Yuanjie Mao, MD, PhD, of the Diabetes Institute, Ohio University, Athens, Ohio, is the corresponding author for the JAMA Oncology article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
