Antidiabetic Effects of the Senolytic Agent Dasatinib.

OBJECTIVE: To evaluate the antidiabetic effects of the senolytic agent dasatinib in older patients with type 2 diabetes mellitus. METHODS: This retrospective cohort study included enterprise-wide Mayo Clinic patients using Informatics for Integrating Biology at the Bedside from January 1994 through December 2019. The antidiabetic outcomes (change in hemoglobin A1c value, serum glucose concentration, and diabetic medications) after 1 year of a strongly senolytic tyrosine kinase inhibitor, dasatinib (n=16), was compared with a weakly senolytic tyrosine kinase inhibitor, imatinib (n=32). RESULTS: Relative to imatinib, patients treated with dasatinib had a mean reduction of 43.7 mg/dL (P=.005) in serum glucose concentration (to convert glucose values to mmol/L, multiply by 0.0555) and required 28.8 fewer total daily insulin units (P=.08) in the setting of a 4.8-kg relative weight loss (5.3% of total body weight; P=.045). Linear regression analysis suggests that the relative difference in weight accounts for 8.4 mg/dL of the 43.7 mg/dL blood glucose value decrease, or 19.2%. Relative to imatinib, patients treated with dasatinib had a mean 0.80 absolute point (P=.05) reduction in hemoglobin A1c and required 18.2 fewer total daily insulin units (P=.16) in the setting of a 5.9-kg relative weight loss (6.3% of total body weight; P=.06). CONCLUSION: Dasatinib may have antidiabetic effects comparable to contemporary diabetic treatments and may be considered for use as a novel diabetic therapy. Future studies are needed to determine whether these results are translatable to patients with type 2 diabetes mellitus without underlying malignant diseases and to determine whether the antidiabetic effects of dasatinib are due to its senolytic properties.

Woman with lower back pain, SIADH and a twist of Lyme.

A 62-year-old woman was admitted with a 3-week history of atraumatic bilateral lower back pain, progressive ascending flaccid paralysis, hyponatraemia and constipation. She was otherwise in good health with only a recent diagnosis of acute gastroenteritis that preceded her presenting symptoms. Her initial laboratory evaluation was consistent with Syndrome of Inappropriate Antidiuretic Hormone (SIADH) but was otherwise unremarkable. MRI of the spine revealed bilateral diffuse nerve root enhancement from at least C6 to the conus level, suggesting an inflammatory process. Lumbar puncture demonstrated high protein (629 mg/dL) with marked pleocytosis (363 cells/mcL) incompatible with albuminocytological dissociation typically seen in Guillain-Barre syndrome. A thorough diagnostic evaluation was undertaken to explore potential infectious, malignant and autoimmune conditions. Lyme disease serology (ELISA and Western Blot, IgM and IgG) was positive leading to a final diagnosis of lymphocytic meningoradiculitis or Bannwarth syndrome.