Cancer incidence in persons with type 1 diabetes: a five-country study of 9,000 cancers in type 1 diabetic individuals

Abstract

Aims/hypothesisAn excess cancer incidence of 20–25% has been identified among persons with diabetes, most of whom have type 2 diabetes. We aimed to describe the association between type 1 diabetes and cancer incidence.MethodsPersons with type 1 diabetes were identified from five nationwide diabetes registers: Australia (2000–2008), Denmark (1995–2014), Finland (1972–2012), Scotland (1995–2012) and Sweden (1987–2012). Linkage to national cancer registries provided the numbers of incident cancers in people with type 1 diabetes and in the general population. We used Poisson models with adjustment for age and date of follow up to estimate hazard ratios for total and site-specific cancers.ResultsA total of 9,149 cancers occurred among persons with type 1 diabetes in 3.9 million person-years. The median age at cancer diagnosis was 51.1 years (interquartile range 43.5–59.5). The hazard ratios (HRs) (95% CIs) associated with type 1 diabetes for all cancers combined were 1.01 (0.98, 1.04) among men and 1.07 (1.04, 1.10) among women. HRs were increased for cancer of the stomach (men, HR 1.23 [1.04, 1.46]; women, HR 1.78 [1.49, 2.13]), liver (men, HR 2.00 [1.67, 2.40]; women, HR 1.55 [1.14, 2.10]), pancreas (men, HR 1.53 [1.30, 1.79]; women, HR 1.25 [1.02,1.53]), endometrium (HR 1.42 [1.27, 1.58]) and kidney (men, HR 1.30 [1.12, 1.49]; women, HR 1.47 [1.23, 1.77]). Reduced HRs were found for cancer of the prostate (HR 0.56 [0.51, 0.61]) and breast (HR 0.90 [0.85, 0.94]). HRs declined with increasing diabetes duration.ConclusionType 1 diabetes was associated with differences in the risk of several common cancers; the strength of these associations varied with the duration of diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-016-3884-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Insulin, insulin receptors, and cancer

“…In that study, linking nationwide diabetes registries from Australia, Denmark Finland, Scotland, and Sweden to national cancer registries, 9149 cancers were identified among persons with T1D. The overall HR for cancer was not increased in men (HR 1.01) and only slightly among women (HR 1.07), but important increases were observed for liver, pancreas, stomach, endometrium, and kidney cancers, resembling the cancer prevalence observed in type 2 diabetics [55]. Previous studies on much smaller series found a higher HR for cancer in T1D patients (HR 1.2) but a similar site-specific involvement [76].…”

“…Recent data from a very large series of T1D patients reported that also in these diabetic patients cancer incidence is increased [55]. In that study, linking nationwide diabetes registries from Australia, Denmark Finland, Scotland, and Sweden to national cancer registries, 9149 cancers were identified among persons with T1D.…”

“…Also type I diabetes, characterized by endogenous insulin deficiency but treated with exogenous either insulin or insulin analogs, often at a dosage that exceeds the normal insulin levels, is associated with increased cancer risk [55].…”

Type 2 Diabetes Mellitus and Cancer: The Role of Pharmacotherapy

“…However, cancer incidence was increased for stomach, liver, pancreas, endometrium, and kidney cancers and was reduced for prostate cancer. 7 These cancers were mostly detected within the first year after diagnosis of T1DM, which suggests a detection bias in those with newly diagnosed T1DM and that long-term hyperglycemia or insulin administration were not contributing to cancer risk. As patients in studies on T1DM tend to be younger than those in studies of T2DM, further studies with longer followup time are needed to understand if T1DM is truly associated with an increase in cancer risk.…”

Perspectives on diabetes mortality as the result of residual confounding and reverse causality by common disease

“…The aforementioned studies primarily focused on T2D. However, a pooled analysis of register data from Danish, Australian, Finnish, Scottish and Swedish patients, interestingly, showed a similar temporal relationship between diagnosis of type 1 diabetes and cancer . In summary, these studies show that duration of diabetes is inversely associated with incidence of cancer; that is, the risk of being diagnosed with cancer is highest among those with a short duration of diabetes.…”