Eliminating exogenous insulin therapy in patients with type 2 diabetes by duodenal ablation and GLP-1RA decreases risk scores for cardiovascular events.

INTRODUCTION: Duodenal Mucosal Resurfacing (DMR) is an endoscopic ablation technique aimed at improving glycaemia and metabolic health in patients with type 2 diabetes mellitus (T2DM). DMR has an insulin sensitizing effect in patients with T2DM. Reducing hyperinsulinemia can improve cardiovascular health. In the INSPIRE trial, we combined a single DMR with a glucagon-like-peptide-1 receptor agonist (GLP-1RA) and demonstrated elimination of insulin treatment in 69% of patients at 6 months and 53% of patients at 18 months while improving glycaemic control and metabolic health. We hypothesized that this treatment approach is associated with improved cardiovascular health, by reducing hyperinsulinemia. METHODS: Before and 6 months after starting the combination treatment to replace insulin, the following assessments were performed to evaluate cardiovascular health: magnetic resonance imaging (MRI) to measure abdominal visceral adipose tissue volume, ambulatory 24 h blood pressure (ABPM) analysis, postprandial insulin and triglycerides, fasting lipid panel and urine microalbumin. The Atherosclerotic Cardiovascular Disease (ASCVD) score was calculated to estimate 10-year risk of cardiovascular disease or stroke and the diabetes lifetime-perspective prediction (DIAL) score was calculated to estimate years free of cardiovascular disease. RESULTS: Six months after replacing exogenous insulin by DMR and GLP-1RA, visceral adipose tissue decreased significantly by 24%. Postprandial triglyceride and insulin concentrations decreased significantly (p < 0.001), as did total cholesterol (from median 3.64 (IQR 3.34-4.89) to 3.48 (3.18-3.97) mmol/l, p = 0.008), LDL (from median 1.92 (IQR 1.49-2.30) to 1.79 (1.49-2.08 mmol/l, p = 0.044), and urine microalbumin (from median 7 (IQR 3-27) to 4 (3-8) mg/l, p = 0.018). All daytime blood pressure values decreased significantly. The ASCVD 10-year risk score decreased (from median 13.6 (IQR 5.7-26.0) to 11.5 (4.2-22.5) %, p = 0.030)) and the DIAL score increased (from median 82 (IQR 81-83) to 83 (81-84) years, (p = 0.039)). DISCUSSION: The combination of DMR and GLP-1RA to replace insulin therapy in patients with T2DM is associated with a positive effect on multiple parameters of cardiovascular health. Taken together, they show a pattern of overall improvement in cardiovascular health, as evidenced by decreased risk scores for cardiovascular complications. However, it is not yet clear whether these improvements will translate into a true reduction in cardiovascular events.

Epidemiology and Etiology of Severe Childhood Encephalitis in The Netherlands.

BACKGROUND: Limited data are available on childhood encephalitis. Our study aimed to increase insight on clinical presentation, etiology, and clinical outcome of children with severe encephalitis in the Netherlands. METHODS: We identified patients through the Dutch Pediatric Intensive Care Evaluation database and included children diagnosed with encephalitis <18 years of age admitted to 1 of the 8 pediatric intensive care units (PICU) in the Netherlands between January 2003 and December 2013. We analyzed demographic characteristics, clinical symptoms, neurologic imaging, etiology, treatment and mortality. RESULTS: We included 121 children with a median age of 4.6 years (IQR 1.3-9.8). The most frequently described clinical features were headache (82.1%), decreased consciousness (79.8%) and seizures (69.8%). In 44.6% of the children, no causative agent was identified. Viral- and immune-mediated encephalitis were diagnosed in 33.1% and 10.7% of the patients. A herpes simplex virus infection (13.2%) was mainly seen in children <5 years of age, median age, 1.73 years (IQR 0.77-5.01), while immune-mediated encephalitis mostly affected older children, median age of 10.4 years (IQR, 3.72-14.18). An age of ≥ 5 years at initial presentation was associated with a lower mortality (OR 0.2 [CI 0.08-0.78]). The detection of a bacterial (OR 9.4 [CI 2.18-40.46]) or viral (OR 3.7 [CI 1.16-11.73]) pathogen was associated with a higher mortality. CONCLUSIONS: In almost half of the Dutch children presenting with severe encephalitis, a causative pathogen could not be identified, underlining the need for enhancement of microbiologic diagnostics. The detection of a bacterial or viral pathogen was associated with a higher mortality.