Peripheral Insulin Extraction in Non-Diabetic Subjects and Type 2 Diabetes Mellitus Patients.

BACKGROUND: Insulin has to be transported across the capillary endothelium to stimulate muscle glucose uptake. We investigated insulin uptake from the peripheral circulation in non-diabetic (ND) individuals and in type 2 diabetes (T2D) patients. METHODS: Single-center cross-sectional study involving 40 ND (age 65±11 years) and 30 T2D patients (age 67±8 years). Thirty-six participants were studied in the fasted state (22 ND subjects and 14 T2D patients termed NDF and T2DF) and 34 participants 1-h following a glucose challenge (18 ND subjects and 16 T2D patients indicated as NDG and T2DG). Main outcome measure was fractional extraction (FE) of insulin (FEins) and glucose using the forearm balance method. RESULTS: In NDF, FEins was 18 (10-26) % at lower insulin levels (63 51-80] pmol/l), while in NDG at higher insulin levels (776 [543-1176] pmol/l), FEins was 9 (4-16) % (p = 0.01 vs. NDF). In NDF only, a negative correlation was observed between FEins and arterial plasma insulin load (rho = - 0.575;p = 0.006) and fasting plasma glucose levels (rho = - 0.551;p = 0.01). In T2DF FEins was 6 (1-19) % and not different from FEins in T2DG (10 2-14) %), and was not associated to fasting glucose. FEins tended to be higher in NDF compared to T2DF (p = 0.07). DISCUSSION: We propose that in ND individuals, besides passive diffusion, an active high-affinity pathway with limited capacity around lower physiologic insulin levels exists for insulin transendothelial transport, contributing to glycemic control. In T2D patients, this mechanism of peripheral insulin uptake is diminished or even absent. Modulation of insulin extraction from the circulation may be a novel target to improve glucose metabolism in T2D.

Prevention of Arrhythmia Device Infection Trial: The PADIT Trial.

BACKGROUND: Infection of implanted medical devices has catastrophic consequences. For cardiac rhythm devices, pre-procedural cefazolin is standard prophylaxis but does not protect against methicillin-resistant gram-positive organisms, which are common pathogens in device infections. OBJECTIVE: This study tested the clinical effectiveness of incremental perioperative antibiotics to reduce device infection. METHODS: The authors performed a cluster randomized crossover trial with 4 randomly assigned 6-month periods, during which centers used either conventional or incremental periprocedural antibiotics for all cardiac implantable electronic device procedures as standard procedure. Conventional treatment was pre-procedural cefazolin infusion. Incremental treatment was pre-procedural cefazolin plus vancomycin, intraprocedural bacitracin pocket wash, and 2-day post-procedural oral cephalexin. The primary outcome was 1-year hospitalization for device infection in the high-risk group, analyzed by hierarchical logistic regression modeling, adjusting for random cluster and cluster-period effects. RESULTS: Device procedures were performed in 28 centers in 19,603 patients, of whom 12,842 were high risk. Infection occurred in 99 patients (1.03%) receiving conventional treatment, and in 78 (0.78%) receiving incremental treatment (odds ratio: 0.77; 95% confidence interval: 0.56 to 1.05; p = 0.10). In high-risk patients, hospitalization for infection occurred in 77 patients (1.23%) receiving conventional antibiotics and in 66 (1.01%) receiving incremental antibiotics (odds ratio: 0.82; 95% confidence interval: 0.59 to 1.15; p = 0.26). Subgroup analysis did not identify relevant patient or site characteristics with significant benefit from incremental therapy. CONCLUSIONS: The cluster crossover design efficiently tested clinical effectiveness of incremental antibiotics to reduce device infection. Device infection rates were low. The observed difference in infection rates was not statistically significant. (Prevention of Arrhythmia Device Infection Trial [PADIT Pilot] [PADIT]; NCT01002911).