Glycaemic control in people with type 2 diabetes mellitus during and after cancer treatment: A systematic review and meta-analysis

Background Cancer and Diabetes Mellitus (DM) are leading causes of death worldwide and the prevalence of both is escalating. People with co-morbid cancer and DM have increased morbidity and premature mortality compared with cancer patients with no DM. The reasons for this are likely to be multifaceted but will include the impact of hypo/hyperglycaemia and diabetes therapies on cancer treatment and disease progression. A useful step toward addressing this disparity in treatment outcomes is to establish the impact of cancer treatment on diabetes control. Aim The aim of this review is to identify and analyse current evidence reporting glycaemic control (HbA1c) during and after cancer treatment. Methods Systematic searches of published quantitative research relating to comorbid cancer and type 2 diabetes mellitus were conducted using databases, including Medline, Embase, PsychINFO, CINAHL and Web of Science (February 2017). Full text publications were eligible for inclusion if they: were quantitative, published in English language, investigated the effects of cancer treatment on glycaemic control, reported HbA1c (%/mmols/mol) and included adult populations with diabetes. Means, standard deviations and sample sizes were extracted from each paper; missing standard deviations were imputed. The completed datasets were analysed using a random effects model. A mixed-effects analysis was undertaken to calculate mean HbA1c (%/mmols/mol) change over three time periods compared to baseline. Results The available literature exploring glycaemic control post-diagnosis was mixed. There was increased risk of poor glycaemic control during this time if studies of surgical treatment for gastric cancer are excluded, with significant differences between baseline and 12 months (p < 0.001) and baseline and 24 months (p = 0.002). Conclusion We found some evidence to support the contention that glycaemic control during and/or after non-surgical cancer treatment is worsened, and the reasons are not well defined in individual studies. Future studies should consider the reasons why this is the case

Tolerance of T-cell clones is associated with membrane antigen changes.

It is possible to regulate the activity of human influenza virus specific helper T-cell clones either by high concentrations of antigen or by anti-idiotypic suppressor T cells. In the absence of accessory cells, the appropriate peptide antigen recognized by the clones induces specific unresponsiveness. This phenomenon, however, is not the result of cytolysis as responsiveness to IL-2 remained unaltered. This suggests that high-dose immunological tolerance need not involve suppressor T cells, and that peptide antigens can interact directly with the T-cell surface. As recent reports suggest that the T-cell surface antigen T3 is involved in the triggering of T lymphocytes and possibly in antigen recognition we have investigated the expression of T3 and other cell surface antigens following the induction of T-cell tolerance. We report here that when a T-cell clone is exposed to a tolerizing concentration of the appropriate peptide antigen, surface T3 antigen is lost in a dose-dependent manner. As loss of surface T3 induced by anti-T3 antibody also results in unresponsiveness to antigen, we conclude that T3 is involved in the process of T-cell triggering by antigen