Study rationale and design of the EANITIATE study (EmpAgliflozin compared to NPH Insulin for sTeroId diAbeTEs) - a randomized, controlled, multicenter trial of safety and efficacy of treatment with empagliflozin compared with NPH-insulin in patients with newly onset diabetes following initiation of glucocorticoid treatment.

BACKGROUND: A well-known metabolic side effect from treatment with glucocorticoids is glucocorticoid-induced diabetes mellitus (GIDM). Guidelines on the management of GIDM in hospitalized patients (in the non-critical care setting), recommend initiation of insulin therapy. The scientific basis and evidence for superiority of insulin therapy over other glucose lowering therapies is however poor and associated with episodes of both hypo- and hyperglycaemia. There is an unmet need for an easier, safe and convenient therapy for glucocorticoid-induced diabetes. METHODS: EANITIATE is a Danish, open, prospective, multicenter, randomized (1:1), parallel group study in patients with new-onset diabetes following treatment with glucocorticoids (> 20 mg equivalent prednisolone dose/day) with blinded endpoint evaluation (PROBE design). Included patients are randomized to either a Sodium-Glucose-Cotransporter 2 (SGLT2) inhibitor or neutral protamin Hagedorn (NPH) insulin and followed for 30 days. Blinded continuous glucose monitoring (CGM) will provide data for the primary endpoint (mean daily blood glucose) and on glucose fluctuations in the two treatment arms. Secondary endpoints are patient related outcomes, hypoglycaemia, means and measures of variation for all values and for time specific glucose values. This is a non-inferiority study with the intent to demonstrate that treatment with empagliflozin is not inferior to treatment with NPH insulin when it comes to glycemic control and side effects. DISCUSSION: This novel approach to management of glucocorticoid-induced hyperglycemia has not been tested before and if SGLT2 inhibition with empaglifozin compared to NPH-insulin is a safe, effective and resource sparing treatment for GIDM, it has the potential to improve the situation for affected patients and have health economic benefits. TRIAL REGISTRATION: www.clinicaltrialsregister.eu no.: 2018-002640-82. Prospectively registered November 20th. 2018. Date of first patient enrolled: June 4th. 2019. This protocol article is based on the EANITATE protocol version 1.3, dated 29. January 2018.

Long-term effects on the progress of neuropathy after diabetic Charcot foot: an 8.5-year prospective case-control study.

OBJECTIVE: Charcot foot is a severe complication to diabetes mellitus, associated with diabetic neuropathy. Any long-term effects of a Charcot foot on the progress of neuropathy are still largely unexplored. The objective was to investigate whether a previous Charcot foot had any long-term effects on the progress of neuropathy. RESULTS: An 8.5-year follow-up case-control study of 49 individuals with diabetes mellitus, 24 of whom also had Charcot foot at baseline visit in 2005-2007. Neuropathy was assessed with a questionnaire, biothesiometry, heart rate variability and venous occlusion plethysmography. Of the 49 baseline participants, 22 were able to participate in the follow-up. Twelve had passed away in the meantime. Heart rate variability was unchanged in both groups; from 9.7 to 7.2 beats/min (p = 0.053) in the Charcot group, and 14.3 to 12.6 beats/min (p = 0.762) in the control group. Somato-sensoric neuropathy showed no difference between baseline and follow-up in the Charcot group (from 39.1 to 38.5 V) (p = 0.946), but a significantly worsened sensitivity in the control group (from 25.1 to 38.9 V) (p = 0.002). In conclusion, we found that any differences in somatic or cardial autonomic neuropathy present at baseline had disappeared at follow-up after 8.5 years.