OBJECTIVE -To determine if glucose management in postcardiothoracic surgery patients with a combined intravenous (IV) and subcutaneous (SC) insulin regimen reduces mortality and morbidity in patients with diabetes and stress-induced hyperglycemia.RESEARCH DESIGN AND METHODS -Retrospective review of 614 consecutive patients who underwent cardiothoracic (CT) surgery in 2005 was performed to evaluate the incidence and treatment of postoperative hyperglycemia and operative morbidity and mortality. Hyperglycemic patients (glucose Ͼ6.05 mmol/l) were treated with IV insulin in the intensive care unit (ICU) followed by SC insulin (outside ICU). Subgroup analysis was performed on 159 coronary artery bypass grafting (CABG)-only patients.RESULTS -Among all CT surgeries, patients with a preoperative diagnosis of diabetes had higher rates of postoperative mortality (7.3 vs. 3.3%; P ϭ 0.03) and pulmonary complications (19.5 vs. 11.6%; P ϭ 0.02) but had similar rates of infections and cardiac, renal, and neurological complications on univariate analysis. However, on multivariate analysis, a preoperative diagnosis of diabetes was not a significant factor in postoperative mortality or pulmonary complications. In CABG-only patients, no significant differences were seen in outcomes between diabetic and nondiabetic patients. Independent of diabetic status, glucose Ն11 mmol/l on ICU admission was predictive of higher rates of mortality and renal, pulmonary, and cardiac postoperative complications.CONCLUSIONS -A combination of IV insulin (in the ICU) and SC insulin (outside the ICU), a less costly and less nursing-intensive therapy than 3 days of IV insulin postoperatively, results in a reduction of the increased surgical morbidity and mortality in diabetic patients after CT surgery. Diabetes Care 30:823-828, 2007

Powers AC. Human islet preparations distributed for research exhibit a variety of insulin-secretory profiles. Am J Physiol Endocrinol Metab 308: E592-E602, 2015. First published February 3, 2015 doi:10.1152/ajpendo.00437.2014.-Human islet research is providing new insights into human islet biology and diabetes, using islets isolated at multiple US centers from donors with varying characteristics. This creates challenges for understanding, interpreting, and integrating research findings from the many laboratories that use these islets. In what is, to our knowledge, the first standardized assessment of human islet preparations from multiple isolation centers, we measured insulin secretion from 202 preparations isolated at 15 centers over 11 years and noted five distinct patterns of insulin secretion. Approximately three quarters were appropriately responsive to stimuli, but one quarter were dysfunctional, with unstable basal insulin secretion and/or an impairment in stimulated insulin secretion. Importantly, the patterns of insulin secretion by responsive human islet preparations (stable Baseline and Fold stimulation of insulin secretion) isolated at different centers were similar and improved slightly over the years studied. When all preparations studied were considered, basal and stimulated insulin secretion did not correlate with isolation center, biological differences of the islet donor, or differences in isolation, such as Cold Ischemia Time. Dysfunctional islet preparations could not be predicted from the information provided by the isolation center and had altered expression of genes encoding components of the glucose-sensing pathway, but not of insulin production or cell death. These results indicate that insulin secretion by most preparations from multiple centers is similar but that in vitro responsiveness of human islets cannot be predicted, necessitating preexperimental human islet assessment. These results should be considered when one is designing, interpreting, and integrating experiments using human islets.human; islet; function THE AVAILABILITY OF HUMAN ISLETS for basic and translational research has increased markedly over the past decade, fueling insights into human islet biology and diabetes. Studies of human islets have provided insight into human islet morphology, ␤-cell proliferation (2, 5, 6, 12), epigenetics (2, 4 -6, 12, 22

Blum RW: Improving transition for adolescents with special health care needs from pediatric to adult-centered health care.

We combined multimodal imaging (bioluminescence, X-ray computed tomography, and PET), tomographic reconstruction of bioluminescent sources, and two unique, complementary models to evaluate three previously synthesized PET radiotracers thought to target pancreatic beta cells. The three radiotracers {[ 18 F]fluoropropyl-(+)-dihydrotetrabenazine ([ 18 F]FP-DTBZ), [ 18 F](+)-2-oxiranyl-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinoline ( 18 F-AV-266), and (2S,3R, 11bR)-9-(3-fluoropropoxy)-2-(hydroxymethyl)-3-isobutyl-10-methoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-ol ( 18 F-AV-300)} bind vesicular monoamine transporter 2. Tomographic reconstruction of the bioluminescent signal in mice expressing luciferase only in pancreatic beta cells was used to delineate the pancreas and was coregistered with PET and X-ray computed tomography images. This strategy enabled unambiguous identification of the pancreas on PET images, permitting accurate quantification of the pancreatic PET signal. We show here that, after conditional, specific, and rapid mouse beta-cell ablation, beta-cell loss was detected by bioluminescence imaging but not by PET imaging, given that the pancreatic signal provided by three PET radiotracers was not altered. To determine whether these ligands bound human beta cells in vivo, we imaged mice transplanted with luciferase-expressing human islets. The human islets were imaged by bioluminescence but not with the PET ligands, indicating that these vesicular monoamine transporter 2-directed ligands did not specifically bind beta cells. These data demonstrate the utility of coregistered multimodal imaging as a platform for evaluation and validation of candidate ligands for imaging islets.diabetes | insulin | molecular imaging | pancreatic islet | bioluminescence tomography

Continuous glucose monitoring (CGM) devices detect more hypo-and hyperglycemic events compared to self-monitoring of blood glucose (SMBG) 1 and are emerging as the standard of care for type 1 diabetes (T1D). 2 CGM devices are also shown to detect activity-related dysglycemia in youth with T1D. 3 However, the physiologic lag in equilibrium between CGM and SMBG of 5-15 minutes may cause a clinically important discrepancy during exercise. 4,5 It remains unclear whether CGM use during exercise suffices for glucose-management decisions. The data presented here examined the concurrent use of two real-time CGM (rtCGM), and one flash glucose monitor (FGM) compared with SMBG during aerobic exercise to determine how these devices could be used effectively to guide carbohydrate intake to avoid hypoglycemia. A male subject with T1D (age 40 years; diabetes duration 25 years; HbA 1c 6.5%) was studied after informed consent was obtained. He wore a hybrid closed loop (HCL) insulin delivery system (Medtronic 670G, Minneapolis, MN; rtCGM1), Dexcom G5® CGM (San Diego, CA; rtCGM2) and Abbott FreeStyle Libre (Chicago, IL; FGM). The FGM and rtCGM devices were inserted 24-48 hours pre-exercise. SMBG was performed using a Contour® Next Link glucose meter (Ascensia Diabetes Care, Parsippany, NJ, USA) according to manufacturer recommendations. The HCL system was placed in "exercise-target" mode 1 hour before, disconnected during, and reconnected immediately after exercise. Pre-exercise meals were consumed >4 hours before activity. The exercise consisted of 1 hour of moderate-intensity running for 13 sessions over two months. Carbohydrate gels were consumed to avoid hypoglycemia during exercise based on the subject's experiences. At exercise onset, glucose levels were higher with FGM (237 ± 45 mg/dL) versus rtCGM1 (198 ± 34 mg/dL), rtCGM2 (206 ± 35 mg/dL), and SMBG (215 ± 33 mg/dL) (all P < .05; Figure 1). SMBG values dropped rapidly during exercise from 215 ± 33 to 104 ± 23 mg/dL (P = .0001),