Diabetic neuropathy: a study on the effects of insulin resistance on its pathophysiology and a randomized clinical trial to prevent neural loss

Descrizione del progetto

Progredire nella comprensione della neuropatia diabetica

La neuropatia diabetica è un tipo di danno ai nervi causato da livelli elevati e prolungati di zucchero nel sangue nei soggetti affetti da diabete. Spesso provoca sintomi come dolore, formicolio e intorpidimento delle estremità, che possono influire significativamente sulla qualità della vita e sulla mobilità. Con il diabete di tipo 2 che sta raggiungendo proporzioni epidemiche, il progetto SenseDiabetes, finanziato dall’UE, mira a sensibilizzare l’opinione pubblica sulla neuropatia diabetica e a migliorare la diagnosi precoce. Gli sforzi si concentreranno sul miglioramento della comprensione della patologia esaminando la resistenza all’insulina nei soggetti affetti da diabete con e senza neuropatia. I ricercatori valuteranno l’efficacia di due diversi farmaci nel trattamento della neuropatia diabetica precoce, studiandone il loro impatto sulla densità e sulla funzione dei nervi.

Obiettivo

We are facing a global epidemic of type 2 diabetes (T2D). Diabetic neuropathy (DN) is the most common complication of T2D affecting ~50% of patients with T2D. If not diagnosed early, DN may lead to further catastrophic complications. However, despite its potentially huge impact on patients’ quality of life, and burden imposed on healthcare systems, patients with T2D and practitioners are often unaware of the manifestations of DN. To make things worse, currently there are no approved treatments for DN.
SenseDiabetes has several aims. First, we wish to increase our knowledge regarding the pathophysiology of DN, specifically assessing whether patients with T2D and DN have worse insulin resistance compared to patients with T2D without DN. While previous studies on DN have shown an effect of insulin resistance on DN, poor indexes of insulin resistance have been used. In SenseDiabetes we will use for the first time the gold standard method for the assessment of insulin resistance, i.e. the euglycemic insulin clamp. Second, we will assess the efficacy of two commonly used antidiabetic drugs in early DN. Patients with T2D and early signs of DN will be randomized to receive treatment for 9 months with either Semaglutide or Empagliflozin. The effects of these drugs on DN outcomes (small fiber density, cardiovascular autonomic function) and advanced glycation end-products will be assessed. Further, we will study with ex vivo experiments the effects of the two drugs of peripheral nerve density (obtained with skin biopsies), and in in vitro experiments we will study the exact mechanisms of action of Semaglutide on cultures of peripheral nerves. Along with the scientific part, SenseDiabetes has a dedicated WP to increase awareness of DN.SenseDiabetes may thus be pivotal for the development of new strategies to combat DN. Also, SenseDiabetes aims to promote awareness of DN and thus increase societal impact through early recognition of DN and prevention of further complications.