Type 1 diabetes and cancer

Although the association between type 2 diabetes is well established, there is considerable overlap between the cancer risks conferred by type 2 diabetes and the associated conditions of obesity and insulin resistance. Meanwhile, there is persisting uncertainty as to the association (if any) between type 1 diabetes and cancer risk. Methodological issues include the younger age and smaller numbers of those with type 1 diabetes, difficulties of classification and increased risk of non-cancer mortality. Although several epidemiological studies have reported associations between type 1 diabetes and overall cancer risk or site-specific cancers, heterogeneity of study methods, populations, entry criteria and outcome measures currently make firm conclusions untenable. On current evidence, it seems likely that any association between type 1 diabetes and cancer is likely to be weak or absent. Much larger studies using standardized methodologies will be needed before any more definitive conclusion can be reached.

Introduction

Type 2 diabetes is associated with increased cancer risk, and this association has been intensively investigated. In contrast, there is still uncertainty as to the association between cancer and type 1 diabetes.

Apart from its obvious clinical relevance, cancer risk in type 1 diabetes should provide insight into cancer risk in type 2 diabetes. This is because type 1 diabetes is not associated with obesity or major insulin resistance, each of which is independently associated with increased cancer risk. It does however entail prolonged exposure both to hyperglycemia and to systemic hyperinsulinemia resulting from the use of injected insulin, thus allowing these potential risk factors to be examined in lean insulin deficient individuals.

Methodological Issues

This analysis has been complicated by a number of methodological difficulties. These include:

  • Type 1 diabetes is less common than type 2, and few study populations are sufficiently large, well characterized and have been followed for a sufficient period of time.

  • Accurate discrimination between type 1 and type 2 diabetes is difficult, and population-based studies are unreliable in this respect.

  • Type 1 diabetes is typically are relatively young when diagnosed and therefore at low risk of cancer.

  • Competing risk also needs to be taken into consideration, since the increased mortality from renovascular disease in type 1 diabetes will be associated with diminished cancer mortality.

Epidemiological Studies

The first of two studies using Swedish data identified people admitted to hospital with a record of type 1 diabetes (defined as first hospital admission with diabetes under 30 years of age) between 1965 and 1999 [1]. There were 355 incident cases of cancer among 29 187 people who had been admitted to hospital with a record of type 1 diabetes, yielding standardised incidence ratios (SIR, (95% confidence interval)) of 1.2(1.0-1.3) for all cancers, 2.3 ( 1.1-4.1)for stomach cancer, 1.6 (1.1 -2.2) for cervical cancer and 2.7(1.4 -4.7) for endometrial cancer. The authors acknowledged the potential for chance findings and the possible of misclassification bias introduced by the inclusion of people with type 2 diabetes in the study.

A second study using Swedish data reported 258 cancers between 1964 to 2006 among 24 052 patients identified from the Hospital Discharge Register (defined as 21 years old or younger at first hospitalization for diabetes)[2]. Elevated SIRs were observed for all cancers ( 1.17 (95% CI 1.04-1.33)), gastric cancer(SIR = 3.32, 95% CI 1.42–6.57) squamous cell skin carcinoma (SIR = 5.09, 95% CI 2.96–8.16) and persisted even after excluding 5 yrs of follow-up for stomach and skin cancer.

A cohort study of members of the British Diabetic Association treated with insulin identified between 1972 and1986 used age under 30 years at diagnosis as the criterion for type 1 diabetes[3]. 214 incident malignancies were identified among the 23 834 participants. The only significant association was an increased incidence (n=16) of ovarian cancer. Age, sex calendar year and country standardised incidence ratios (95% confidence interval) were 0.95 (0.84–1.08) and 2.14 (1.22–3.48) for all cancers andovarian cancer respectively.

Site-specific cancers

A systematic review identified 39 cases of pancreatic cancer among people with type 1 and young-onset diabetes from three cohorts (including those mentioned above) and six case–control studies[4] (9) and reported that the relative risk for pancreatic cancer in people with diabetes was 2.00 (95% confidence interval 1.37–3.01) compared to those without diabetes. The authors acknowledge the small numbers of outcomes (only two of the nine studies had data on more than five people with pancreatic cancer) and the possible contamination of the estimates by the inclusion of people with type 2 diabetes if age at diagnosis alone is used to identify people with type 1 diabetes.

The authors concluded that risk of pancreatic cancer appeared to be similarly elevated in people with both type 1 and type 2 diabetes and that larger studies of people with type 1 diabetes together with a non-diabetic comparison group would be needed to confirm this finding.

Literature Reviews

A recent literature review of the epidemiological evidence linking type 1 diabetes to cancer risk found inconsistent results[5]. The analysis located 22 eligible studies. Case-control studies found no association between the two conditions, cohort studies produced mixed results, whereas two meta-analyses found some positive associations. Analytical findings also varied according to definition of type 1 diabetes and region.

The authors considered that meta-analysis would be inappropriate in the light of the diversity of endpoints and heterogeneity of both methods and findings that they encountered, thus opting for a narrative review. They conclude that, on present evidence, any association between type 1 diabetes and cancer is likely to be either weak or absent. Much larger studies with standardized methodology and criteria for the diagnosis of type 1 diabetes will be needed to reach a more definitive conclusion.

References

  1. ^ Zendehdel K et al. Cancer incidence in patients with type 1 diabetes mellitus: a population-based cohort study in Sweden. J Natl Cancer Inst 2003;95:1797-800.

  2. ^ Shu X et al. Cancer risk among patients hospitalized for type 1 diabetes mellitus: a population-based cohort study in Sweden. Diabet Med 2010 Jul;27(7):791-7.

  3. ^ Swerdlow AJ et al. Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study. Br J Cancer 2005 Jun 6;92(11):2070-5.

  4. ^ Stevens RJ et al. Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta-analysis. Br J Cancer 2007 Feb 12;96(3):507-9.

  5. ^ Gordon-Dseagu VL et al. Epidemiological evidence of a relationship between type 1 diabetes mellitus and cancer: a review of the existing literature. Int J Cancer 2013;132:501-8

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