1. Figure 2 Clinical vignette and putative causal relationships
between obesity, diabetes, antidiabetic medications, cancer, and cancer treatments
Figure 2 | Clinical vignette and putative causal relationships between obesity, diabetes, antidiabetic medications, cancer, and cancer treatments. a | A hypothetical patient with obesity, type 2 diabetes mellitus (T2DM), and breast cancer is depicted. Treatment for early stage breast cancer is commenced on the background of dual antidiabetic therapy with metformin and a sulfonylurea (SU). Further dysglycaemia leads to metformin, thiazolidinedione (TZD), and a dipeptidyl peptidase-4 inhibitor (DPP4i) triple therapy for T2DM, with continuation of adjuvant hormonal therapy for breast cancer. When liver metastases are diagnosed and hyperglycaemia worsens, metformin and TZD are withdrawn; chemotherapy and irradiation are then administered as anticancer therapy, and long-acting (LA) insulin is prescribed to achieve better glycaemic control. Following the diagnosis of brain metastases, the patient is given steroids, necessitating the addition of short-acting (SA) insulin to antidiabetic therapy (with DPPi withdrawal). b | The directed acyclic schematic depicts the possible causal relationships between obesity, T2DM, antidiabetic medications, cancer, and cancer treatments. Obesity is associated with increased mortality in general, but can also lead to T2DM and, possibly, cancer, which further increase morbidity and mortality. Cancer and cancer treatment influence the progression and treatment of T2DM, and possibly vice versa. An example of a hypothesized interaction is the reduction of breast-cancer risk associated with metformin treatment of T2DM. An example of a known clinical interaction is that steroid treatments for brain metastases or chemotherapy-induced vomiting can lead to increased insulin requirements in patients with insulin-dependent diabetes and cancer. BMI, body mass index; HbA1c, haemoglobin A1c (glycated haemoglobin).
Klil-Drori, A. J. et al. (2016) Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing?
Nat. Rev. Clin. Oncol. doi: /nrclinonc