Long-acting insulin analogs and cancer
| Autor: | Andrea Tumminia, Sebastiano Squatrito, Laura Sciacca, Riccardo Vigneri, Lucia Frittitta, A. Belfiore, Veronica Vella, Livia Manzella |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Blood Glucose Time Factors Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Decision-Making Medicine (miscellaneous) Insulin Glargine 030209 endocrinology & metabolism Pharmacology Risk Assessment 03 medical and health sciences 0302 clinical medicine Risk Factors Diabetes mellitus Hyperinsulinism Neoplasms Hyperinsulinemia medicine Diabetes Mellitus Animals Humans Hypoglycemic Agents Insulin detemir Nutrition and Dietetics biology business.industry Insulin glargine Insulin Incidence Cancer medicine.disease Insulin receptor 030104 developmental biology Treatment Outcome biology.protein Cardiology and Cardiovascular Medicine business Biomarkers medicine.drug |
| Popis: | Aims Hyperinsulinemia is a recognized risk factor for cancer and plays a major role for the increased cancer incidence in diabetic patients. Whether insulin analogs, and particularly long-acting analogs, worsen the pro-cancer effect of excess insulin is still controversial. Data synthesis In this paper we summarize the biological bases for the potential detrimental effect of long-acting analogs on cancer cells and review the in vitro and in vivo evidence on this issue. Because of their different molecular structure relative to native insulin, insulin analogs may activate the insulin receptor (IR) and the post receptor pathways differently. Most, but not all, in vitro evidence indicate that long-acting analogs may have a stronger mitogenic potency than insulin on cancer cells. Notably insulin glargine, the most studied long-acting analog, also has a higher affinity for the insulin-like growth factor (IGF)-1 receptor, a potent growth mediator. In vitro observations, however, may not reflect what occurs in vivo when analogs are metabolized to derivatives with a different mitogenic activity. Clinical studies, mostly retrospective and predominantly concerning glargine, provide contrasting results. The only perspective trial found no cancer increase in patients treated with glargine. All these studies, however, have severe weaknesses because of the insufficient evaluation of important factors such as dose administered, length of exposure, patient follow-up duration and site-specific cancer investigation. Moreover, whether cancer promotion is a long-acting analog class characteristic or a specific effect of a single agent is not clear. Conclusions In conclusion the carcinogenic risk of long-acting analogs, and specifically glargine, can be neither confirmed nor excluded. A personalized and shared decision, considering all the individual risk factors (metabolic and non-metabolic), is the suggestion for the clinician. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|