Dr Sorin Herscovici, Sermo member and Endocrinologist, reports on some of the new diabetes research presented at the American Diabetes Association’s 75th Scientific Sessions.
The morning ADA diabetes care symposium mentioned new drug classes : Sotaglifozin, a first in class dual SGLT1 and2 inhibitor. Used in type 1 DM as 400 mg once daily, it improved glycemic control in intensively treated patients(read with insulin) after 28 days. Patients were able to decrease bolus and mealtime insulin as well as A1c. Hypoglycemia incidence did not increase. Of note, both patients on CSII and on MDI participated in the trial. DKA was seen in 2 cases believed to be secondary to pump failure. However As it was mentioned in another session(see below ADA day 3) , cases of euglycemic DKA have been described with SGLT2 inhibitors. Nausea still persists with sotaglifozin.
Ranolazine, an antianginal drug previously approved in 2006 and its mechanism is slow sodium channel inhibition in themyocardium (slowsodium channels are with increased activation in the ischemic myocardium) has also been lately shown to have hypoglycemic action mainly through glucagon inhibition. It decrease A1c by ~ 0.6% when used as monotherapy and by 0.5 % when used in combo with metformin and glimepiride.
Mary de Groot’s session on Depression, Distress and Glycemia, was very interesting showing a study from South London, UK which explored inflammatory markers present in Diabetics with depression. The higher the depressive symptom scale, the higher the inflammatory markers.
Trang Ly presented a study involving Integrated Medtronic hybrid closed loop system in type 1 DM at Diabetes Camp achieved nocturnal control in 80% of cases in range but failed to show superiority when compared to the classic Medtronic 530 G pump with Threshold suspend. Dr ly stated “perhaps most importantly were changes to the user interface with data obtained from patient usability studies.” This study will lead to new algorithms of study desin for pump therapy.
The afternoon session ” debating the value of new insulins in the mgmt of T2DM chaired by Bergenstahl and Nathan was very stimulating exploring the new insulins like Degludec (not FDA approved) and Toujeo (FDA approved) which are 2 new basal insulins with extended duration of action and less hypoglycemia incidence than Levemir and Lantus respectively. Another insulin discussed was the hepatoselective pegylated insulin developed by Eli Lilly not yet FDA approved wich is supposedly lasting 36 hours, but can potentially mildly increase the liver enzymes (AST, ALT) and decrease hepatic glucose utilization. Where do we use them? The pegylated could find use in renal failure patients, the other two in patients not well controlled with the basal insulins currently available
The Joint ADA/ASN symposium ” anew day for diabetic kidney disease ” explored the genetic polymorphisms encountered in kidney transplant recipients (TCFL2, Diabetogenic effect of tacrolimus could be mediatedby its effect on mitochondrial function- mitochondrial haplogroup H more frequent in PTDM OR 1.82, KNNJ11 polymorphism,). Obesity and the risk for kidney transplantation was shown (BMI 25-30. Had 1.4 fold increased risk and BMI> 30 had 2 fold increased risk). Race : AA, native american, hispanic have higher incidence of PTDM.
If IFG or IGT was detected pre-transplant, there was 58% PTDM incidence (ptdm= posttransplant diabetes), metabolic syndrome HR 2.6 PTDM and HbA1c OR 4.63. Another risk factor for PTDM was HCV seropositive status (OR 3.75) and another was CMV even asymptomatic.
The immunosuppressive drugs were then reviewed (CSS, calcineurin inhibitors, sirolimus, azathioprine, mycophenolate mofetil). For cyclosporin: decreased pancreatic insulin content, decreased beta cell volume, islet cell toxicity, decreased insulin release. For tacrolimus: insulin RNAm transcription defect, increased levels of FK506 BP12 in Beta cell. Dose dependent effect (tacrolimus> 15 ng/ml 1 st month associated with increased risk of IGT (15%) and PTDM (32%). Both cyclosporin A and dirolimus induce insulin resistance by acting on adipocyte, liver and muscle, leading to TG levels, decreasing glucose transport genes in the adipocyte and increasing gluconeogenic genes in the liver
How can we prevent PTDM: risk stratification, lifestyle modification, pretransplant HCV , tailored imunosuppresion, beta cell protection. For risk stratification: age> 50;pretransplant BMI > 30, pretransplant FPG> 100, planned CSS maintenance post T; fam hx t2dm,pre-T TG> 200; pre-T use of gout medicine
Dr Sorin Herscovici is currently the Chief of Endocrinology at Manchester VAMC in Manchester, NH and affiliated with Dartmouth Medical School(Medicine) as well as Northeastern University (Pharmacy) and MCPH (Pharmacy). He also manages a very busy Endocrine Practice that is about 80 percent Diabetes that runs a comprehensive Diabetes management program and an Insulin pump program that contains pumps from different manufacturers (Medtronic, Animas, Dexcom CGM). Dr Herscovici is currently involved in teaching some of the clinical sessions for pharmacy students affiliated with the above mentioned Universities. He am ABIM Certified in Endocrinology, Diabetes and Metabolism.