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New systemic cancer therapies are increasingly oriented towards specific signaling pathways involved in carcinogenesis. However, these new treatments may lead to disorders of glycemic homeostasis ranging from glucose intolerance, diabetes or the occurrence of severe acute hyperglycemic syndrome due to blockade of certain pathways common to glucose metabolism. This article discusses the estimated frequency of new-onset diabetes, the pathophysiological mechanisms as well as the diagnostic, therapeutic, monitoring and prognostic management of glycemic dysfunction in patients treated with these novel systemic cancer therapies.

Post-transplantation diabetes (PTDM) exposes to increased morbidity (cardiovascular or infectious complications, early graft dysfunction) and to a risk of premature death. Recognition of risk factors is essential for early and individualized care. The management of a PTDM requires the use of oral antidiabetic treatments (metformin or DPP4 inhibitors) or GLP1 receptor agonists for their favorable effects on weight and kidney that seem ideal in this context. Corticosteroid-induced diabetes or the rare occurrence of diabetic ketoacidosis require insulin therapy. In the long term, the main objective remains to integrate PTDM treatment in a more comprehensive management, targeting the reduction of cardiovascular risk of vulnerable transplant patients.

Based on the epidemiological data currently available, diabetes does not seem to be a risk factor for infection with SARS-CoV-2 but may be associated with a more severe course. Diabetes is extremely common in older patients with co-morbidities who are at risk of unfavorable outcomes. As with any other infection, poorly controlled pre-existing diabetes can promote secondary infections and lead to acute complications related to hyperglycemia, worsened itself by the infection. It is important to advise patients to have enough diabetic equipment and supplies at home, to make regular blood glucose self-tests, and to contact a caregiver immediately in case of glycemic imbalance or signs of infection. Antidiabetic therapy may need adjustments following usual sick day rules. Insulin therapy should be considered to treat any persistent hyperglycemia in patients hospitalized for an acute infection.

Hypoglycemia is a potentially serious complication of insulin therapy. Some insulin-dependent diabetic patients can benefit from continuous subcutaneous insulin infusion therapy (an "insulin pump"), which in most case improves glycemia control and decreases the occurrence of hypoglycemic episodes. However, such events may occur, particularly during initial treatment phases or pregnancy. Severe hypoglycemia is mainly managed by stopping the insulin pump and insuring an adequate carbohydrate intake. Patients with insulin pumps and their entourage should receive specific instruction in the adjustment of pump flow in the presence of dysglycemia-inducing circumstances (illness, physical exertion), as well as in anticipation of high-risk situations, such as motor-vehicle driving.

Insulin treatment is associated with two important and frequent side effects: hypoglycemia and weight gain. Weight gain is in contradiction with the physiological central effect of insulin which leads to decreased food intake like leptin. However, decreased urinary caloric loss due to better glycemic control, prevention and correction of hypoglycemia, the anabolic effect of insulin and the possible central resistance to insulin explain the observed weight gain. Insulin is often necessary when oral antidiabetic treatment fails; the physician and the patient need to remain alert to minimize the side effects through adequate insulin regimen and life style.

Several insulin analogues have been developed in recent years and are increasingly being used in the treatment of diabetes. However, modifying the insulin molecule not only changes its metabolic effects, but can also alter its mitogenic potency. In vitro experiments had previously suggested a potential association between insulin analogues and cancer. In 2009 several articles were published in Diabetologia describing an association between administration of glargine (Lantus) and higher incidence of cancer rates. The present article aims at briefly presenting the state of the art based upon currently available data on insulin and cancer. We will summarize the mechanisms by which insulin can increase cell proliferation, the observations reported in recent publications and finally conclude with some practical recommendations.